Journal of Neurology & Neuromedicine

BACKGROUND: While clinical studies have documented sex differences in emotional, behavioral, and cognitive function of children with Attention Deficit and Hyperactive Disorder (ADHD), it is unknown if these sex differences are due to differences in referral and diagnosis or if they can be also seen when we screen a community sample for ADHD. If these sex differences exist in populations with a diagnosis history but cannot be seen in screening, then they are unfair, preventable, and due to gender (social processes in referral and diagnosis) rather than sex...

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Growing evidence highlights the intimate relationship between type II diabetes (T2D) and Alzheimer's disease (AD). Importantly, these two diseases share a number of pathological similarities, including amyloid accumulation, oxidative stress, inflammation, and cell death. To date, drug therapies for AD and T2D are lacking and there is a crucial need for the discovery and development of novel therapeutics for these diseases. A number of human and rodent studies have given evidence that metabolic hormone supplementation is highly valuable for improving cognitive function and overall metabolic health in both T2D and AD...

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No abstract text is available yet for this article.

Gulf War Illness (GWI) is a chronic debilitating disease of unknown etiology that affects the brain and has afflicted many veterans of the 1990-91 Gulf War (GW). We showed recently1 that blood serum from patients suffering from GWI exerts detrimental effects on neural cultures, including reduced growth, increased apoptosis, and disruption of neural network function. Remarkably, these adverse effects were prevented by the concomitant addition to the culture of serum from healthy Gulf War (GW) era veterans. We interpreted those findings1 in the context of our hypothesis that GWI is, at least partly, due to circulating pathogenic persistent antigens2 , probably coming from vaccines administered to GW veterans who lacked crucial Human Leukocyte Antigen (HLA) class 2 alleles3 and, therefore, could not make antibodies against those antigens; by contrast, healthy GW veterans who received the same vaccines and possessed HLA protection3 made antibodies that neutralized the various antigens...

Gulf War Illness (GWI) is a chronic debilitating disease of unknown etiology that affects the brain and has afflicted many veterans of the 1990-91 Gulf War (GW). Here we tested the hypothesis that brain damage may be caused by circulating harmful substances to which GW veterans were exposed but which could not be eliminated due to lack of specific immunity. We assessed the effects of serum from GWI patients on function and morphology of brain cultures in vitro, including cultures of embryonic mouse brain and neuroblastoma N2A line...

GWI has affected a substantial number of Gulf War (GW) veterans. The disease involves several organ systems among which the brain is most prominent. Neurological, cognitive and mood-related (NCM) symptoms frequently dominate and are at the root of chronic ill-health and disability in veterans suffering from GWI. In addition, such symptoms frequently co-occur with diagnosable mental health disorders, predominantly posttraumatic stress disorder (PTSD). Here we investigated the possibility that increased GWI severity leads, above a threshold, to a diagnosable mental health disorder (excluding psychosis)...

Daily rhythms in behavior and physiology are coordinated by an endogenous clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. This central pacemaker also relays day length information to allow for seasonal adaptation, a process for which melatonin signaling is essential. How the SCN encodes day length is not fully understood. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by directing target mRNAs for degradation or translational repression. The miR-132/212 cluster plays a key role in facilitating neuronal plasticity, and miR-132 has been shown previously to modulate resetting of the central clock...

The cerebellar ataxias are a group of incurable brain disorders that are caused primarily by the progressive dysfunction and degeneration of cerebellar Purkinje cells. The lack of reliable disease models for the heterogeneous ataxias has hindered the understanding of the underlying pathogenic mechanisms as well as the development of effective therapies for these devastating diseases. Recent advances in the field of induced pluripotent stem cell (iPSC) technology offer new possibilities to better understand and potentially reverse disease pathology...

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Malignant cerebral edema is a potential consequence of large territory cerebral infarction, as the resultant elevation in intracranial pressure may progress to transtentorial herniation, brainstem compression, and death. In appropriate patients, decompressive hemicraniectomy (DHC) reduces mortality without increasing the risk of severe disability. However, as the foundational DHC randomized, controlled trials excluded patients greater than 60 years of age, the appropriateness of DHC in older adults remains controversial...

Long-distance intracellular axonal transport is predominantly microtubule-based, and its impairment is linked to neurodegeneration. Here we review recent theoretical and experimental evidence that suggest that near the axon boundaries (walls), the effective viscosity can become large enough to impede cargo transport in small (but not large) caliber axons. Theoretical work suggests that this opposition to motion increases rapidly as the cargo approaches the wall. However, having parallel microtubules close enough together to enable a cargo to simultaneously engage motors on more than one microtubule dramatically enhances motor activity, and thus decreases the effects due to such opposition...

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Nitric oxide derived from endothelial nitric oxide synthase (eNOS) has been shown to be a major mediator of endothelium-dependent responses in cerebral blood vessels. Loss of a single eNOS gene is not associated with any apparent negative consequences on endothelial function in most blood vessels. In contrast, we have recently demonstrated that heterozygous eNOS gene deficiency in combination with a high fat diet is associated with marked impairment of endothelial function. These findings provide an important example of eNOS haploinsufficiency and one that directly impacts the cerebral vasculature...

The human dopamine transporter (hDAT) belongs to the solute carrier 6 (SLC6) gene family. Point mutations in hDAT (SLC6A3) have been linked to a syndrome of dopamine transporter deficiency or infantile dystonia/parkinsonism. The mutations impair DAT folding, causing retention of variant DATs in the endoplasmic reticulum and subsequently impair transport activity. The folding trajectory of DAT itself is not understood, though many insights have been gained from studies of folding-deficient mutants of the closely related serotonin transporter (SERT); i...

Alzheimer's disease (AD) is characterized by neuronal death with an accumulaton of intra-cellular neurofibrillary tangles (NFT) and extracellular amyloid plaques. Reduced DNA repair ability has been reported in AD brains. In neurons, the predominant mechanism to repair double-strand DNA breaks (DSB) is non-homologous end joining (NHEJ) that requires DNA-dependent protein kinase (DNA-PK) activity. DNA-PK is a holoenzyme comprising the p460 kD DNA-PK catalytic subunit (DNA-PKcs) and its activator Ku, a heterodimer of p86 (Ku80) and p70 (Ku70) subunits...

Parkinson's disease (PD) is a neurodegenerative disorder of the central nervous system with a clinically heterogeneous presentation that includes progressive loss of dopaminergic (DA) neurons in the substantia nigra. A minority of PD cases are familial and are caused by mutations in single genes. Most cases, however, are idiopathic PD, a complex multifactorial disorder with environmental and genetic contributors to etiology. Here, we first briefly summarize published evidence that among environmental contributors is dietary deficiency of magnesium...

The brain is a complex system that requires continual regulation of parenchymal pressure, osmolarity, and waste removal for optimal function; despite this, human brain lacks any obvious extension of lymphatic circulation for moderating fluid and waste regulation. We recapitulate herein a recent analysis of proteinaceous waste deposition in the human brain, its observed route of clearance, and the implications of abnormal accumulation along this clearance pathway as a potential mechanism of neurological diseases...

Deep brain stimulation (DBS) has proven to be an effective treatment for neurologic disorders such as Parkinson's disease, and is currently being investigated as a therapy for psychiatric diseases such as addiction, major depressive disorder, and obsessive compulsive disorder. In this commentary, we review and discuss the findings presented in the Letter to the Editor entitled "Attitudes towards treating addiction with deep brain stimulation," written by Ali et al(1). The survey presented in this Letter reported general approval for examining the effects of DBS on addictive disorders in a clinical trial, but highlighted critical areas of concern including informed consent, patient autonomy, appropriate medical practice, passing of clinical trial milestones, and implications on law enforcement...