Excitatory-inhibitory imbalance in Alzheimer's disease and therapeutic significance.
Abstract The interplay between excitatory and inhibitory circuits underlies the brain's processes and their dysregulation has been linked to cognitive decline, psychiatric disorders and epilepsy. In patients with Alzheimer's disease (AD), an elevated occurrence of seizures has been observed in both sporadic and familial forms of the condition. Although seizure activity in AD has been mainly viewed as a result of neuronal cell loss and considered to occur in later stages, it is now becoming increasingly clear that aberrant neuronal activity may be more common in patients at earlier stages than previously thought an...
Source: Neurobiology of Disease - April 15, 2019 Category: Neurology Authors: Varela EV, Etter G, Williams S Tags: Neurobiol Dis Source Type: research

Sleep, oscillations, interictal discharges, and seizures in human focal epilepsy.
This article discusses the influence of sleep on adult focal epilepsy as assessed objectively via EEG, and highlights new developments of the last decade regarding sleep microstructure and new markers of the epileptogenic zone such as high-frequency oscillations>80 Hz. It further describes evidence obtained from invasive intracranial EEG, as this is a unique measure to assess directly cortical activity of superficial and deep structures of the human brain. Important achievements of the last decade were to unravel how epileptic activity is modulated by sleep, underlining the role of sleep slow waves to enhance epileptic ...
Source: Neurobiology of Disease - April 11, 2019 Category: Neurology Authors: Frauscher B, Gotman J Tags: Neurobiol Dis Source Type: research

Ablation of the pro-inflammatory master regulator miR-155 does not mitigate neuroinflammation or neurodegeneration in a vertebrate model of Gaucher's disease.
Abstract Bi-allelic mutations in the glucocerebrosidase gene (GBA1) cause Gaucher's disease, the most common human lysosomal storage disease. We previously reported a marked increase in miR-155 transcript levels and early microglial activation in a zebrafish model of Gaucher's disease (gba1-/-). miR-155 is a master regulator of inflammation and has been implicated in a wide range of different neurodegenerative disorders. The observed miR-155 upregulation preceded the subsequent development of widespread pathology with marked neuroinflammation, closely resembling human Gaucher's disease pathology. We now report sim...
Source: Neurobiology of Disease - April 11, 2019 Category: Neurology Authors: Watson L, Keatinge M, Gegg M, Bai Q, Sandulescu C, Vardi A, Futerman AH, Schapira AHV, Burton EA, Bandmann O Tags: Neurobiol Dis Source Type: research

Therapeutic potential of a TrkB agonistic antibody for ischemic brain injury.
Abstract The clinical trials employing neuroprotectants targeting single, early pathogenic mechanisms in stroke have so far been barely successful. We found in human postmortem stroke brains that in addition to apoptosis, necroptosis also contributed to neuronal damage. Thus, a new strategy targeting both mechanisms might be necessary. While brain-derived neurotrophic factor (BDNF) is a potent survival factor for neurons, its poor bioavailability including low diffusion rate and short half-life makes it unlikely a therapeutic agent. We recently developed a TrkB agonistic antibody (Ab4B19) that mimicked BDNF functi...
Source: Neurobiology of Disease - April 11, 2019 Category: Neurology Authors: Han F, Guan X, Guo W, Lu B Tags: Neurobiol Dis Source Type: research

Cardiorespiratory profiling reveals primary breathing dysfunction in Kcna1-null mice: Implications for sudden unexpected death in epilepsy.
Abstract Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality, but the relative importance of underlying cardiac and respiratory mechanisms remains unclear. To illuminate the interactions between seizures, respiration, cardiac function, and sleep that contribute to SUDEP risk, here we developed a mouse epilepsy monitoring unit (EMU) to simultaneously record video, electroencephalography (EEG), electromyography (EMG), plethysmography, and electrocardiography (ECG) in a commonly used genetic model of SUDEP, the Kcna1 knockout (Kcna1-/-) mouse. During interictal periods, Kcna...
Source: Neurobiology of Disease - April 8, 2019 Category: Neurology Authors: Dhaibar H, Gautier NM, Chernyshev OY, Dominic P, Glasscock E Tags: Neurobiol Dis Source Type: research

A Parkinson's disease gene, DJ-1, regulates anti-inflammatory roles of astrocytes through prostaglandin D2 synthase expression.
Abstract Dysfunctional regulation of inflammation may contribute to the progression of neurodegenerative diseases. The results of this study revealed that DJ-1, a Parkinson's disease (PD) gene, regulated expression of prostaglandin D2 synthase (PTGDS) and production of prostaglandin D2 (PGD2), by which DJ-1 enhanced anti-inflammatory function of astrocytes. In injured DJ-1 knockout (KO) brain, expression of tumor necrosis factor-alpha (TNF-α) was more increased, but that of anti-inflammatory heme oxygenase-1 (HO-1) was less increased compared with that in injured wild-type (WT) brain. Similarly, astrocyte-co...
Source: Neurobiology of Disease - April 4, 2019 Category: Neurology Authors: Choi DJ, An J, Jou I, Park SM, Joe EH Tags: Neurobiol Dis Source Type: research

An integrated transcriptomics and proteomics analysis reveals functional endocytic dysregulation caused by mutations in LRRK2.
CONCLUSIONS: Our study demonstrates extensive alterations across the endocytic pathway associated with LRRK2 mutations in iPSC-derived dopaminergic neurons and BAC transgenic rats, as well as in post-mortem brain tissue from PD patients carrying a LRRK2 mutation. In particular, we find evidence of disrupted clathrin-mediated endocytosis and suggest that LRRK2-mediated PD pathogenesis may arise through dysregulation of this process. PMID: 30954703 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - April 4, 2019 Category: Neurology Authors: Connor-Robson N, Booth H, Martin JG, Gao B, Li K, Doig N, Vowles J, Browne C, Klinger L, Juhasz P, Klein C, Cowley SA, Bolam P, Hirst W, Wade-Martins R Tags: Neurobiol Dis Source Type: research

Heritability and genetic variance of dementia with Lewy bodies.
A, Morenas-Rodriguez E, Clark L, Honig LS, Marder K, Lemstra A, Rogaeva E, St George-Hyslop P, Londos E, Zetterberg H, Barber I, Braae A, Brown K, Morgan K, Troakes C, Al-Sarraj S, Lashley T, Holton J, Compta Y, Van Deerlin V, Serrano GE, Beach TG, Lesage S, Galasko D, Masliah E, Santana I, Pastor P, Diez-Fairen M, Aguilar M, Tienari PJ, Myllykangas L, Oinas M, Revesz T, Lees A, Boeve BF, Petersen RC, Ferman TJ, Graff-Radford N, Cairns NJ, Morris JC, Pickering-Brown S, Mann D, Halliday GM, Hardy J, Trojanowski JQ, Dickson DW, Singleton A, International Parkinson's Disease Genomics Consortium, Stone DJ, Bras J Abstract...
Source: Neurobiology of Disease - April 3, 2019 Category: Neurology Authors: Guerreiro R, Escott-Price V, Hernandez DG, Kun-Rodrigues C, Ross OA, Orme T, Neto JL, Carmona S, Dehghani N, Eicher JD, Shepherd C, Parkkinen L, Darwent L, Heckman MG, Scholz SW, Troncoso JC, Pletnikova O, Dawson T, Rosenthal L, Ansorge O, Clarimon J, Lle Tags: Neurobiol Dis Source Type: research

Curcumin restores innate immune Alzheimer's disease risk gene expression to ameliorate Alzheimer pathogenesis.
We report effects of low (Curc-lo) and high (Curc-hi) doses of curcumin on neuroinflammation in APPsw transgenic mice. Results showed that Curc-lo decreased CD33 and increased TREM2 expression (predicted to decrease AD risk) and also increased TyroBP, which controls a neuroinflammatory gene network implicated in AD as well as phagocytosis markers CD68 and Arg1. Curc-lo coordinately restored tightly correlated relationships between these genes' expression levels, and decreased expression of genes characteristic of toxic pro-inflammatory M1 microglia (CD11b, iNOS, COX-2, IL1β). In contrast, very high dose curcumin did n...
Source: Neurobiology of Disease - April 2, 2019 Category: Neurology Authors: Teter B, Morihara T, Lim GP, Chu T, Jones MR, Zuo X, Paul RM, Frautschy SA, Cole GM Tags: Neurobiol Dis Source Type: research

Quantitative ultrasound and apoptotic death in the neonatal primate brain.
We report for the first time in vivo changes in QUS parameters, which may reflect severity of apoptosis in the brains of infant nonhuman primates. These findings suggest that QUS may enable in vivo studies of apoptosis in the brains of human infants following exposure to anesthetics, antiepileptics and other brain injury mechanisms. PMID: 30951850 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - April 2, 2019 Category: Neurology Authors: Rosado-Mendez IM, Noguchi KK, Castañeda-Martinez L, Kirvassilis G, Wang SH, Manzella F, Swiney BS, Masuoka K, Capuano S, Brunner KG, Crosno K, Guerrero QW, Whitson H, Brambrink A, Simmons HS, Mejia AF, Zagzebski JA, Hall TJ, Ikonomidou C Tags: Neurobiol Dis Source Type: research

Corrigendum to "Neuron and neuroblast numbers and cytogenesis in the dentate gyrus of aged APPswe/PS1dE9transgenic mice: Effect of long-term treatment with paroxetine" [Neurobiol Dis. 2017; 104: 50-60].
Corrigendum to "Neuron and neuroblast numbers and cytogenesis in the dentate gyrus of aged APPswe/PS1dE9transgenic mice: Effect of long-term treatment with paroxetine" [Neurobiol Dis. 2017; 104: 50-60]. Neurobiol Dis. 2019 Apr;124:573 Authors: Olesen LØ, Sivasaravanaparan M, Severino M, Babcock AA, Bouzinova EV, West MJ, Wiborg O, Finsen B PMID: 30717840 [PubMed - in process] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - February 6, 2019 Category: Neurology Authors: Olesen LØ, Sivasaravanaparan M, Severino M, Babcock AA, Bouzinova EV, West MJ, Wiborg O, Finsen B Tags: Neurobiol Dis Source Type: research

Synergistic action of CB1 and 5-HT2B receptors in preventing pilocarpine-induced status epilepticus in rats.
Abstract Endocannabinoids (eCBs) and serotonin (5-HT) play a neuromodulatory role in the central nervous system. Both eCBs and 5-HT regulate neuronal excitability and their pharmacological potentiation has been shown to control seizures in pre-clinical and human studies. Compelling evidence indicates that eCB and 5-HT systems interact to modulate several physiological and pathological brain functions, such as food intake, pain, drug addiction, depression, and anxiety. Nevertheless, there is no evidence of an eCB/5-HT interaction in experimental and human epilepsies, including status epilepticus (SE). Here, we perf...
Source: Neurobiology of Disease - February 1, 2019 Category: Neurology Authors: Colangeli R, Di Maio R, Pierucci M, Deidda G, Casarrubea M, Di Giovanni G Tags: Neurobiol Dis Source Type: research

Maternal immune activation impairs cognitive flexibility and alters transcription in frontal cortex.
CONCLUSIONS: These findings suggest that MIA can lead to impairments in cognitive flexibility in mice similar to those exhibited in ASD individuals, and that these impairments are associated with altered gene expression in frontal cortex. PMID: 30716470 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - February 1, 2019 Category: Neurology Authors: Amodeo DA, Lai CY, Hassan O, Mukamel EA, Behrens MM, Powell SB Tags: Neurobiol Dis Source Type: research

Mannitol decreases neocortical epileptiform activity during early brain development via cotransport of chloride and water.
Abstract Seizures and brain injury lead to water and Cl- accumulation in neurons. The increase in intraneuronal Cl- concentration ([Cl-]i) depolarizes the GABAA reversal potential (EGABA) and worsens seizure activity. Neocortical neuronal membranes have a low water permeability due to the lack aquaporins necessary to move free water. Instead, neurons use cotransport of ions including Cl- to move water. Thus, increasing the extracellular osmolarity during seizures should result in an outward movement of water and salt, reducing [Cl-]i and improving GABAA receptor-mediated inhibition. We tested the effects of hypero...
Source: Neurobiology of Disease - January 31, 2019 Category: Neurology Authors: Glykys J, Duquette E, Rahmati N, Duquette K, Staley KJ Tags: Neurobiol Dis Source Type: research

Insights into GBA Parkinson's disease pathology and therapy with induced pluripotent stem cell model systems.
Abstract While the link between GBA and Parkinson's disease (PD) was initially unexpected, it is now well established that GBA mutations are the most frequent genetic risk for PD. GBA has also been linked to sporadic PD, dementia with Lewy bodies, and ageing. Thus, GBA represents a promising target to counteract brain disease and the age-related decline of lysosomal function. The exact mechanisms involved in the risk of developing PD in GBA mutation carriers are still unclear and research in this field has faced the major challenge of a lack of proper modeling systems. Induced pluripotent stem cells (iPSCs) as wel...
Source: Neurobiology of Disease - January 31, 2019 Category: Neurology Authors: Baden P, Yu C, Deleidi M Tags: Neurobiol Dis Source Type: research

Multi-faceted therapeutic strategy for treatment of Alzheimer's disease by concurrent administration of etodolac and α-tocopherol.
In conclusion, this study highlights the significance of combination therapy to simultaneously target multiple disease pathways, and suggest the repurposing and combination of etodolac and α-tocopherol as a novel therapeutic strategy against AD. PMID: 30710675 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - January 30, 2019 Category: Neurology Authors: Elfakhri KH, Abdallah IM, Brannen AD, Kaddoumi A Tags: Neurobiol Dis Source Type: research

Role of pedunculopontine nucleus in sleep-wake cycle and cognition in humans: A systematic review of DBS studies.
PMID: 30710676 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - January 30, 2019 Category: Neurology Authors: Ricciardi L, Sarchioto M, Morgante F Tags: Neurobiol Dis Source Type: research

Trihexyphenidyl rescues the deficit in dopamine neurotransmission in a mouse model of DYT1 dystonia.
Abstract Trihexyphenidyl, a nonselective muscarinic receptor antagonist, is the small molecule drug of choice for the treatment of DYT1 dystonia, but it is poorly tolerated due to significant side effects. A better understanding of the mechanism of action of trihexyphenidyl is needed for the development of improved treatments. Because DTY1 dystonia is associated with both abnormal cholinergic neurotransmission and abnormal dopamine regulation, we tested the hypothesis that trihexyphenidyl normalizes striatal dopamine release in a mouse model of DYT1 dystonia using ex vivo fast scan cyclic voltammetry and in vivo m...
Source: Neurobiology of Disease - January 29, 2019 Category: Neurology Authors: Downs AM, Fan X, Donsante C, Jinnah HA, Hess EJ Tags: Neurobiol Dis Source Type: research

MiR-146a promotes oligodendrocyte progenitor cell differentiation and enhances remyelination in a model of experimental autoimmune encephalomyelitis.
This study provides insight into the cellular and molecular bases for the therapeutic effects of miR-146a on OPC differentiation and remyelination, and suggests the potential of enhancing miR-146a as a treatment of demyelinating disorders. PMID: 30707940 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - January 29, 2019 Category: Neurology Authors: Zhang J, Zhang ZG, Lu M, Zhang Y, Shang X, Chopp M Tags: Neurobiol Dis Source Type: research

Neuronal overexpression of Alzheimer's disease and down's syndrome associated DYRK1A/minibrain gene alters motor decline, neurodegeneration and synaptic plasticity in Drosophila.
Abstract Down syndrome (DS) is characterised by abnormal cognitive and motor development, and later in life by progressive Alzheimer's disease (AD)-like dementia, neuropathology, declining motor function and shorter life expectancy. It is caused by trisomy of chromosome 21 (Hsa21), but how individual Hsa21 genes contribute to various aspects of the disorder is incompletely understood. Previous work has demonstrated a role for triplication of the Hsa21 gene DYRK1A in cognitive and motor deficits, as well as in altered neurogenesis and neurofibrillary degeneration in the DS brain, but its contribution to other DS ph...
Source: Neurobiology of Disease - January 28, 2019 Category: Neurology Authors: Lowe SA, Usowicz MM, Hodge JJL Tags: Neurobiol Dis Source Type: research

Cannabinoid type-1 receptor blockade restores neurological phenotypes in two models for Down syndrome.
cute;guez-Moreno A, Maldonado R, Ozaita A Abstract Intellectual disability is the most limiting hallmark of Down syndrome, for which there is no gold-standard clinical treatment yet. The endocannabinoid system is a widespread neuromodulatory system involved in multiple functions including learning and memory processes. Alterations of this system contribute to the pathogenesis of several neurological and neurodevelopmental disorders. However, the involvement of the endocannabinoid system in the pathogenesis of Down syndrome has not been explored before. We used the best-characterized preclinical model of Down syndr...
Source: Neurobiology of Disease - January 24, 2019 Category: Neurology Authors: Navarro-Romero A, Vázquez-Oliver A, Gomis-González M, Garzón-Montesinos C, Falcón-Moya R, Pastor A, Martín-García E, Pizarro N, Busquets-Garcia A, Revest JM, Piazza PV, Bosch F, Dierssen M, de la Torre R, Rodríguez-Moreno A, Maldonado R, Ozaita A Tags: Neurobiol Dis Source Type: research

Child maltreatment and psychosis.
Abstract This paper reviews the literature on the association between experiences of child abuse and neglect and the development of psychoses. It then explores the premise that psychotic patients with a history of maltreatment may comprise a clinically and biological distinct subgroup. The review demonstrates that there is a growing consensus in the field that experiences of child maltreatment contribute to the onset of psychotic symptoms and psychotic disorders. There is also strong support for the premise that patients with psychotic disorders and histories of child maltreatment have distinct clinical characteri...
Source: Neurobiology of Disease - January 24, 2019 Category: Neurology Authors: Kaufman J, Torbey S Tags: Neurobiol Dis Source Type: research

TDP-43 proteinopathy in aging: Associations with risk-associated gene variants and with brain parenchymal thyroid hormone levels.
Abstract TDP-43 proteinopathy is very common among the elderly (affecting at least 25% in individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n...
Source: Neurobiology of Disease - January 22, 2019 Category: Neurology Authors: Nelson PT, Gal Z, Wang WX, Niedowicz DM, Artiushin SC, Wycoff S, Wei A, Jicha GA, Fardo DW Tags: Neurobiol Dis Source Type: research

The role of pallidum in the neural integrator model of cervical dystonia.
Abstract Dystonia is the third most common movement disorder affecting three million people worldwide. Cervical dystonia is the most common form of dystonia. Despite common prevalence the pathophysiology of cervical dystonia is unclear. Traditional view is that basal ganglia is involved in pathophysiology of cervical dystonia, while contemporary theories suggested the role of cerebellum and proprioception in the pathophysiology of cervical dystonia. It was recently proposed that the cervical dystonia is due to malfunctioning of the head neural integrator - the neuron network that normally converts head velocity to...
Source: Neurobiology of Disease - January 21, 2019 Category: Neurology Authors: Sedov A, Usova S, Semenova U, Gamaleya A, Tomskiy A, Crawford JD, Corneil B, Jinnah HA, Shaikh AG Tags: Neurobiol Dis Source Type: research

Increased anxiety-like behavior following circuit-specific catecholamine denervation in mice.
Abstract Parkinson's disease (PD) presents with a constellation of non-motor symptoms, notably increased anxiety, which are currently poorly treated and underrepresented in animal models of the disease. Human post-mortem studies report loss of catecholaminergic neurons in the pre-symptomatic phases of PD when anxiety symptoms emerge, and a large literature from rodent and human studies indicate that catecholamines are important mediators of anxiety via their modulatory effects on limbic regions such as the amygdala. On the basis of these observations, we hypothesized that anxiety in PD could result from an early l...
Source: Neurobiology of Disease - January 21, 2019 Category: Neurology Authors: Ferrazzo S, Gunduz-Cinar O, Stefanova N, Pollack GA, Holmes A, Schmuckermair C, Ferraguti F Tags: Neurobiol Dis Source Type: research

Brain insulin response and peripheral metabolic changes in a Tau transgenic mouse model.
Abstract Accumulation of hyper-phosphorylated and aggregated Tau proteins is a neuropathological hallmark of Alzheimer's Disease (AD) and Tauopathies. AD patient brains also exhibit insulin resistance. Whereas, under normal physiological conditions insulin signaling in the brain mediates plasticity and memory formation, it can also regulate peripheral energy homeostasis. Thus, in AD, brain insulin resistance affects both cognitive and metabolic changes described in these patients. While a role of Aβ oligomers and APOE4 towards the development of brain insulin resistance emerged, contribution of Tau pathology ...
Source: Neurobiology of Disease - January 18, 2019 Category: Neurology Authors: Leboucher A, Ahmed T, Caron E, Tailleux A, Raison S, Joly-Amado A, Marciniak E, Carvalho K, Hamdane M, Bantubungi K, Lancel S, Eddarkaoui S, Caillierez R, Vallez E, Staels B, Vieau D, Balschun D, Buee L, Blum D Tags: Neurobiol Dis Source Type: research

The α3 and α4 nicotinic acetylcholine receptor (nAChR) subunits in the brainstem medulla of sudden infant death syndrome (SIDS).
This study focuses on the α3 and α4 nAChR subunits as α3 is important for early postnatal survival while α4 is crucial for nicotine-elicited antinociception and sleep-wake cycle regulation. Tissue from the rostral medulla of infants who died with a known cause of death (eSUDI, n = 7), and from SIDS classified as SIDS I (n = 8) and SIDS II (n = 27), was immunohistochemically stained for the α3 and α4 nAChR subunits and quantified in 9 nuclei comparing amongst these groups. The association with risk factors of sex, cigarette smoke exposure, upper respiratory tract infection (UR...
Source: Neurobiology of Disease - January 18, 2019 Category: Neurology Authors: Aishah A, Hinton T, Waters KA, Machaalani R Tags: Neurobiol Dis Source Type: research

N-Palmitoylethanolamine-oxazoline (PEA-OXA): A new therapeutic strategy to reduce neuroinflammation, oxidative stress associated to vascular dementia in an experimental model of repeated bilateral common carotid arteries occlusion.
CONCLUSION: Thus, the modulation of intracellular NAAA by PEA-OXA could offer a novel means of controlling neuroinflammatory conditions associated with VaD. PMID: 30660740 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - January 17, 2019 Category: Neurology Authors: Impellizzeri D, Siracusa R, Cordaro M, Crupi R, Peritore AF, Gugliandolo E, D'Amico R, Petrosino S, Evangelista M, Di Paola R, Cuzzocrea S Tags: Neurobiol Dis Source Type: research

A two-hit story: Seizures and genetic mutation interaction sets phenotype severity in SCN1A epilepsies.
Abstract SCN1A (NaV1.1 sodium channel) mutations cause Dravet syndrome (DS) and GEFS+ (which is in general milder), and are risk factors in other epilepsies. Phenotypic variability limits precision medicine in epilepsy, and it is important to identify factors that set phenotype severity and their mechanisms. It is not yet clear whether SCN1A mutations are necessary for the development of severe phenotypes or just for promoting seizures. A relevant example is the pleiotropic R1648H mutation that can cause either mild GEFS+ or severe DS. We used a R1648H knock-in mouse model (Scn1aRH/+) with mild/asymptomatic phenot...
Source: Neurobiology of Disease - January 16, 2019 Category: Neurology Authors: Salgueiro-Pereira AR, Duprat F, Pousinha P, Loucif A, Douchamps V, Regondi C, Ayrault M, Eugie M, Stunault MI, Escayg A, Goutagny R, Gnatkovsky V, Frassoni C, Marie H, Bethus I, Mantegazza M Tags: Neurobiol Dis Source Type: research

Maternal immune activation-induced PPAR γ-dependent dysfunction of microglia associated with neurogenic impairment and aberrant postnatal behaviors in offspring.
Maternal immune activation-induced PPARγ-dependent dysfunction of microglia associated with neurogenic impairment and aberrant postnatal behaviors in offspring. Neurobiol Dis. 2019 Jan 16;: Authors: Zhao Q, Wang Q, Wang J, Tang M, Huang S, Peng K, Han Y, Zhang J, Liu G, Fang Q, You Z Abstract Maternal infection during pregnancy is an important factor involved in the pathogenesis of brain disorders in the offspring. Mounting evidence from maternal immune activation (MIA) animals indicates that microglial priming may contribute to neurodevelopmental abnormalities in the offspring. Because peroxiso...
Source: Neurobiology of Disease - January 16, 2019 Category: Neurology Authors: Zhao Q, Wang Q, Wang J, Tang M, Huang S, Peng K, Han Y, Zhang J, Liu G, Fang Q, You Z Tags: Neurobiol Dis Source Type: research

Long-term RNAi knockdown of α-synuclein in the adult rat substantia nigra without neurodegeneration.
Long-term RNAi knockdown of α-synuclein in the adult rat substantia nigra without neurodegeneration. Neurobiol Dis. 2019 Jan 15;: Authors: Zharikov A, Bai Q, De Miranda BR, Van Laar A, Timothy Greenamyre J, Burton EA Abstract α-Synuclein plays a central role in the pathogenesis of Parkinson's disease (PD); interventions that decrease its expression appear neuroprotective in PD models. Successful translation of these observations into effective therapies will be dependent on the safety of suppressing α-synuclein expression in the adult brain. We investigated long-term α-synuclei...
Source: Neurobiology of Disease - January 15, 2019 Category: Neurology Authors: Zharikov A, Bai Q, De Miranda BR, Van Laar A, Timothy Greenamyre J, Burton EA Tags: Neurobiol Dis Source Type: research

Integrative analysis of blood metabolomics and PET brain neuroimaging data for Parkinson's disease.
CONCLUSION: Integrating blood metabolomics data combined with PET data considerably enhances the diagnostic discrimination power. Metabolomic signatures also indicate interesting disease-inherent changes in cellular processes, including oxidative stress response and inflammation. PMID: 30639291 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - January 9, 2019 Category: Neurology Authors: Glaab E, Trezzi JP, Greuel A, Jäger C, Hodak Z, Drzezga A, Timmermann L, Tittgemeyer M, Diederich NJ, Eggers C Tags: Neurobiol Dis Source Type: research

Local cortical circuit correlates of altered EEG in the mouse model of Fragile X syndrome.
In conclusion, hyperactivity and increased gamma activity in local neocortical circuits, together with increased gamma synchrony between circuits, provide a putative substrate for EEG alterations observed in both FXS patients and the FXS mouse model. PMID: 30639292 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - January 8, 2019 Category: Neurology Authors: Goswami S, Cavalier S, Sridhar V, Huber KM, Gibson JR Tags: Neurobiol Dis Source Type: research

Human and rodent temporal lobe epilepsy is characterized by changes in O-GlcNAc homeostasis that can be reversed to dampen epileptiform activity.
Abstract Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder. O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a PTM occurring at serine/threonine residues that is derived from and closely associated with metabolic substrates. The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification. The goal of this study was to characterize OGT/OGA and protein O-GlcNAcylation in the epileptic hippocampus and to determine and whether direct ...
Source: Neurobiology of Disease - January 6, 2019 Category: Neurology Authors: Sanchez RG, Ryley Parrish R, Rich M, Webb WM, Lockhart RM, Nakao K, Ianov L, Buckingham SC, Broadwater DR, Jenkins A, de Lanerolle NC, Cunningham M, Eid T, Riley K, Lubin FD Tags: Neurobiol Dis Source Type: research

Assessment of diets containing curcumin, epigallocatechin-3-gallate, docosahexaenoic acid and α-lipoic acid on amyloid load and inflammation in a male transgenic mouse model of Alzheimer's disease: Are combinations more effective?
Assessment of diets containing curcumin, epigallocatechin-3-gallate, docosahexaenoic acid and α-lipoic acid on amyloid load and inflammation in a male transgenic mouse model of Alzheimer's disease: Are combinations more effective? Neurobiol Dis. 2019 Jan 02;: Authors: Sharman MJ, Gyengesi E, Liang H, Chatterjee P, Karl T, Li QX, Wenk MR, Halliwell B, Martins RN, Müench G Abstract Increasingly, evidence is accumulating pointing at a protective role of a healthy diet at decreasing the risk of Alzheimer's disease. To test the effectiveness of nutritional components, the following food-derived ...
Source: Neurobiology of Disease - January 2, 2019 Category: Neurology Authors: Sharman MJ, Gyengesi E, Liang H, Chatterjee P, Karl T, Li QX, Wenk MR, Halliwell B, Martins RN, Müench G Tags: Neurobiol Dis Source Type: research

Decreased circulating ErbB4 ectodomain fragments as a read-out of impaired signaling function in amyotrophic lateral sclerosis.
This study assesses whether soluble proteolytic fragments of the ErbB4 ectodomain (ecto-ErbB4) can be detected in cerebrospinal fluid (CSF) and plasma, and if the levels are altered in ALS. Immunoprecipitation combined with mass spectrometry or western blotting analyses confirmed the presence of ecto-ErbB4 in human CSF. Several anti-ErbB4-reactive bands, including a 55 kDa fragment, were detected in CSF. The bands were generated in the presence of neuregulin-1 (Nrg1) and were absent in plasma from ErbB4 knockout mice. Ecto-ErbB4 levels were decreased in CSF from ALS patients (n = 20) and ALS with concomitant frontote...
Source: Neurobiology of Disease - December 27, 2018 Category: Neurology Authors: Lopez-Font I, Sogorb-Esteve A, Javier-Torrent M, Brinkmalm G, Herrando-Grabulosa M, García-Lareu B, Turon-Sans J, Rojas-García R, Lleó A, Saura CA, Zetterberg H, Blennow K, Bosch A, Navarro X, Sáez-Valero J Tags: Neurobiol Dis Source Type: research

Pridopidine stabilizes mushroom spines in mouse models of Alzheimer's disease by acting on the sigma-1 receptor.
We report here that pridopidine and 3-PPP protect mushroom spines from Aβ42 oligomer toxicity in primary WT hippocampal cultures from mice. Pridopidine also reversed LTP defects in hippocampal slices resulting from application of Aβ42 oligomers. Pridopidine and 3-PPP rescued mushroom spines in hippocampal cultures from APP-KI and PS1-KI mice. S1R knockdown from lenti-viral shRNA expression destabilized WT mushroom spines and prevented the synaptoprotective effects of pridopidine in PS1-KI cultures. Knockout of PS1/2 destabilized mushroom spines and pridopidine was unable to prevent this. Pridopidine lowered endop...
Source: Neurobiology of Disease - December 27, 2018 Category: Neurology Authors: Ryskamp D, Wu L, Wu J, Kim D, Rammes G, Geva M, Hayden M, Bezprozvanny I Tags: Neurobiol Dis Source Type: research

Mutant SOD1 prevents normal functional recovery through enhanced glial activation and loss of motor neuron innervation after peripheral nerve injury.
This study identified a relationship between genetic and environmental contributions to disease onset and progression in ALS. The findings suggest that injury induced SOD1 mutant protein induces a heightened and prolonged inflammatory response resulting in motor neuron degeneration through synaptic loss. Once initiated, this process spreads to adjacent motor neurons leading to contiguous spread of the disease. Treatments that suppress this heightened glial response could slow disease progression in ALS patients with focal sites of disease onset. SIGNIFICANCE STATEMENT: The contribution of environmental factors such as...
Source: Neurobiology of Disease - December 27, 2018 Category: Neurology Authors: Schram S, Chuang D, Schmidt G, Piponov H, Helder C, Kerns J, Gonzalez M, Song F, Loeb JA Tags: Neurobiol Dis Source Type: research

Rho-kinase inhibition has antidepressant-like efficacy and expedites dendritic spine pruning in adolescent mice.
Abstract Adolescence represents a critical period of neurodevelopment, defined by structural and synaptic pruning within the prefrontal cortex. While characteristic of typical development, this structural instability may open a window of vulnerability to developing neuropsychiatric disorders, including depression. Thus, therapeutic interventions that support or expedite neural remodeling in adolescence may be advantageous. Here, we inhibited the neuronally-expressed cytoskeletal regulatory factor Rho-kinase (ROCK), focusing primarily on the clinically-viable ROCK inhibitor fasudil. ROCK inhibition had rapid antide...
Source: Neurobiology of Disease - December 26, 2018 Category: Neurology Authors: Shapiro LP, Kietzman HW, Guo J, Rainnie DG, Gourley SL Tags: Neurobiol Dis Source Type: research

Diving responses elicited by nasopharyngeal irrigation mimic seizure-associated central apneic episodes in a rat model.
Abstract The spread of epileptic seizure activity to brainstem respiratory and autonomic regions can elicit episodes of obstructive apnea and of central apnea with significant oxygen desaturation and bradycardia. Previously, we argued that central apneic events were not consequences of respiratory or autonomic activity failure, but rather an active brainstem behavior equivalent to the diving response resulting from seizure spread. To test the similarities of spontaneous seizure-associated central apneic episodes to evoked diving responses, we used nasopharyngeal irrigation with either cold water or mist for 10 or ...
Source: Neurobiology of Disease - December 25, 2018 Category: Neurology Authors: Mooney S, Chin B, Villiere S, Nakase K, Kollmar R, Kim S, Sundaram K, Silverman JB, Lazar J, Stewart M Tags: Neurobiol Dis Source Type: research

Low cerebral blood flow is a non-invasive biomarker of neuroinflammation after repetitive mild traumatic brain injury.
Abstract Previous work has shown that non-invasive optical measurement of low cerebral blood flow (CBF) is an acute biomarker of poor long-term cognitive outcome after repetitive mild traumatic brain injury (rmTBI). Herein, we explore the relationship between acute cerebral blood flow and underlying neuroinflammation. Specifically, because neuroinflammation is a driver of secondary injury after TBI, we hypothesized that both glial activation and inflammatory signaling are associated with acute CBF and, by extension, with long-term cognitive outcome after rmTBI. To test this hypothesis, cortical CBF was non-invasiv...
Source: Neurobiology of Disease - December 25, 2018 Category: Neurology Authors: Sankar SB, Pybus AF, Liew A, Sanders B, Shah KJ, Wood LB, Buckley EM Tags: Neurobiol Dis Source Type: research

Changes of dimension of EEG/ECoG nonlinear dynamics predict epileptogenesis and therapy outcomes.
i A Abstract The lack of early biomarkers of epileptogenesis precludes a sound prediction of epilepsy development after acute brain injuries and of the natural course of the disease thus impairing the development of antiepileptogenic treatments. We investigated whether the dimensional changes of nonlinear dynamics in EEG/ECoG signals, that were recorded in the early aftermath of different epileptogenic injuries, provide a measure to be exploited as a sensitive prognostic and predictive biomarker for epilepsy. Using three different models of epilepsy in two rodent species, we report a common and significant decreas...
Source: Neurobiology of Disease - December 24, 2018 Category: Neurology Authors: Rizzi M, Brandt C, Weissberg I, Milikovsky DZ, Pauletti A, Terrone G, Salamone A, Frigerio F, Löscher W, Friedman A, Vezzani A Tags: Neurobiol Dis Source Type: research

High-frequency oscillations and focal seizures in epileptic rodents.
oli M Abstract High-pass filtering (> 80 Hz) of EEG signals has enabled neuroscientists to analyze high-frequency oscillations (HFOs; i.e., ripples: 80-200 Hz and fast ripples: 250-500 Hz) in epileptic patients presenting with focal seizures and in animal models mimicking this condition. Evidence obtained from these studies indicate that HFOs mirror pathological network activity that may initiate and sustain ictogenesis and epileptogenesis. HFOs are observed in temporal lobe regions of epileptic animals during interictal periods but they also occur before seizure onset and during the ictal period, suggest...
Source: Neurobiology of Disease - December 24, 2018 Category: Neurology Authors: Lévesque M, Avoli M Tags: Neurobiol Dis Source Type: research

Brain proteome changes in female Brd1+/- mice unmask dendritic spine pathology and show enrichment for schizophrenia risk.
In this study, we applied label-based quantitative mass spectrometry to profile the frontal cortex, hippocampus and striatum proteome and synaptosomal proteome of female Brd1+/- mice. We successfully quantified between 1537 and 2196 proteins and show widespread changes in protein abundancies and compartmentalization. By integrative analysis of human genetic data, we find that the differentially abundant proteins in frontal cortex and hippocampus are enriched for schizophrenia risk further linking the actions of BRD1 to psychiatric disorders. Affected proteins were further enriched for proteins involved in processes known t...
Source: Neurobiology of Disease - December 24, 2018 Category: Neurology Authors: Paternoster V, Svanborg M, Edhager AV, Rajkumar AP, Eickhardt EA, Pallesen J, Grove J, Qvist P, Fryland T, Wegener G, Nyengaard JR, Mors O, Palmfeldt J, Børglum AD, Christensen JH Tags: Neurobiol Dis Source Type: research

Cell injury and receptor expression in the epileptic human amygdala.
Abstract Neuropathological findings in the amygdala obtained from patients with mesial temporal lobe epilepsy (MTLE) indicate varying degrees of histopathological alterations, such as neuronal loss and gliosis. The mechanisms underlying cellular damage in the amygdala of patients with MTLE have not been fully elucidated. In the present study, we assess cellular damage, determine the receptor expression of major inhibitory and excitatory neurotransmitters, and evaluate the correlation between the expression of various receptors and cell damage in the basolateral complex and the centromedial areas in the amygdala sp...
Source: Neurobiology of Disease - December 24, 2018 Category: Neurology Authors: Jafarian M, Mousavi SMM, Alipour F, Aligholi H, Noorbakhsh F, Ghadipasha M, Gharehdaghi J, Kellinghaus C, Kovac S, Ghadiri MK, Meuth SG, Speckmann EJ, Stummer W, Gorji A Tags: Neurobiol Dis Source Type: research

Neural correlates of cognitive deficits across developmental phases of schizophrenia.
Abstract Schizophrenia is associated with cognitive deficits across all stages of the illness (i.e., high risk, first episode, early and chronic phases). Identifying the underlying neurobiological mechanisms of these deficits is an important area of scientific inquiry. Here, we selectively review evidence regarding the pattern of deficits across the developmental trajectory of schizophrenia using the five cognitive domains identified by the Research Domain Criteria (RDoC) initiative. We also report associated findings from neuroimaging studies. We suggest that most cognitive domains are affected across the develop...
Source: Neurobiology of Disease - December 21, 2018 Category: Neurology Authors: Kelly S, Guimond S, Lyall A, Stone WS, Shenton ME, Keshavan M, Seidman LJ Tags: Neurobiol Dis Source Type: research

Chronic stress-induced gut dysfunction exacerbates Parkinson's disease phenotype and pathology in a rotenone-induced mouse model of Parkinson's disease.
Abstract Recent evidence provides support for involvement of the microbiota-gut-brain axis in Parkinson's disease (PD) pathogenesis. We propose that a pro-inflammatory intestinal milieu, due to intestinal hyper-permeability and/or microbial dysbiosis, initiates or exacerbates PD pathogenesis. One factor that can cause intestinal hyper-permeability and dysbiosis is chronic stress which has been shown to accelerate neuronal degeneration and motor deficits in Parkinsonism rodent models. We hypothesized that stress-induced intestinal barrier dysfunction and microbial dysbiosis lead to a pro-inflammatory milieu that ex...
Source: Neurobiology of Disease - December 20, 2018 Category: Neurology Authors: Dodiya HB, Forsyth CB, Voigt RM, Engen PA, Patel J, Shaikh M, Green SJ, Naqib A, Roy A, Kordower JH, Pahan K, Shannon KM, Keshavarzian A Tags: Neurobiol Dis Source Type: research

Cinnamic acid activates PPAR α to stimulate Lysosomal biogenesis and lower Amyloid plaque pathology in an Alzheimer's disease mouse model.
In this study, we demonstrate that cinnamic acid, a naturally occurring plant-based product, induces lysosomal biogenesis in mouse primary brain cells via upregulation of TFEB. We delineate that cinnamic acid activates the nuclear hormone receptor PPARα to transcriptionally upregulate TFEB and stimulate lysosomal biogenesis. Moreover, using in-silico and biochemical approaches we established that cinnamic acid serves as a potent ligand for peroxisome proliferator-activated receptor α (PPARα). Finally, cinnamic acid treatment in male and female 5× Familial Alzheimer's disease (5XFAD) mice remarkably ...
Source: Neurobiology of Disease - December 19, 2018 Category: Neurology Authors: Chandra S, Roy A, Jana M, Pahan K Tags: Neurobiol Dis Source Type: research

Activation of enkephalinergic (Enk) interneurons in the central amygdala (CeA) buffers the behavioral effects of persistent pain.
Abstract Enk neurons in CeA modulate the activity of the amygdala projection neurons and it is very likely that changes of Enk signaling cause the heightened anxiety that accompanies chronic pain. We use chemogenetics and transgenic mice to investigate the effects of acute and continuous activation of the amygdala Enk neurons on persistent pain and anxiodepressive-like behavior in mice. Enk-cre mice were injected bilaterally into the CeA with cre-activated AAV-DREADD/Gq/mCherry, while neuropathic pain was induced by sciatic nerve constriction. A single injection of DREADD's ligand CNO decreased the anxiety-like be...
Source: Neurobiology of Disease - December 17, 2018 Category: Neurology Authors: Paretkar T, Dimitrov E Tags: Neurobiol Dis Source Type: research

Cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying β-amyloid pathology.
Cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying β-amyloid pathology. Neurobiol Dis. 2018 Dec 14;: Authors: Diouf I, Fazlollahi A, Bush AI, Ayton S, Alzheimer's disease Neuroimaging Initiative Abstract β-Amyloid pathology is elevated in ~30% of cognitively normal people over 65, and is associated with accelerated neurodegeneration in the pre-clinical stages of Alzheimer's disease. Recent findings reveal that brain iron might also act to propel neurodegeneration in people with underlying amyloid pathology. Here, repeated PET scans of fluorodeoxyglucos...
Source: Neurobiology of Disease - December 14, 2018 Category: Neurology Authors: Diouf I, Fazlollahi A, Bush AI, Ayton S, Alzheimer's disease Neuroimaging Initiative Tags: Neurobiol Dis Source Type: research