Neuroscience
-
Growing evidence suggests Attention Deficit Hyperactivity Disorder (ADHD) often co-occurs with Autism Spectrum Disorder (ASD), and a better understanding of the nature of their overlap, including at a neurobiological level, is needed. Research has implicated cerebellar-networks as part of the neural-circuitry disrupted in ASD, but little research has been carried out to investigate this in ADHD. We investigated cerebellar integrity using a double-step saccade adaptation paradigm in a group of male children age 8-15 (n=12) diagnosed with ADHD-Combined Type (-CT). ⋯ Greater saccadic gain change (adaptation) was also positively correlated with higher Movement ABC-2 total and balance scores among the ADHD-CT participants. These differences suggest cerebellar networks underlying saccade adaptation may be disrupted in young people with ADHD-CT. Though our findings require further replication with larger samples, they suggest further research into cerebellar dysfunction in ADHD-CT, and as a point of neurobiological overlap with ASD, may be warranted.
-
Vitamin D regulates multiple factors including those involved in the ontogeny of dopaminergic systems. It has been shown that in neonatal rats maternally deprived of vitamin D, dopamine (DA) turnover is decreased with associated reductions in one catabolic enzyme, catechol-o-methyl transferase (COMT). To directly examine this signaling relationship, in the present study we have over-expressed the vitamin D receptor (VDR) in neuroblastoma SH-SY5Y cells in order to examine the mechanisms by which the active vitamin D hormone, 1,25(OH)2D3, via its receptor VDR, affects DA production and turnover. ⋯ Chromatin immunoprecipitation revealed that 1,25(OH)2D3 increased VDR binding in three regions of the COMT promoter, strongly suggesting direct regulation. In addition, 1,25(OH)2D3 treatment attenuated increased levels of MAOA, DRD2 and VMAT2 gene expression caused by the VDR-overexpression. Taken together, these results show VDR and 1,25(OH)2D3 are directly involved in regulating the expression of dopaminergic-associated genes and that this in vitro neuronal model is a useful tool for identifying the role of 1,25(OH)2D3 in DA neuronal development and maturation.
-
Small molecular G-protein plays a key role in several diseases. This study was designed to reveal the role of RhoA signaling in the pathophysiology of neuropathic pain in mice. Partial sciatic nerve injury caused thermal hyperalgesia, mechanical allodynia, and increased plasma membrane translocation of RhoA in the lumber spinal cord. ⋯ Pharmacological inhibition of ROCK also attenuated the increased expression of GFAP-ir and phosphorylated MARCKS-ir. Together, it is suggested that astrogliosis initiated by the activation of RhoA/ROCK signaling results in MARCKS phosphorylation in nerve terminals, which leads to hyperalgesia in neuropathic pain. Furthermore, simvastatin exerts antihyperalgesic and antiallodynic effects through the inhibition of spinal RhoA activation.
-
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accompanied by memory deficits and neuropsychiatric dysfunction. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have seemly therapeutic potential in AD, but the benefit of n-3 PUFAs is still in debates. Here, we employed a transgenic mice carry fat-1 gene to encode n-3 desaturase from Caenorhabditis elegans, which increase endogenous n-3 PUFAs by converting n-6 PUFAs to n-3 PUFAs crossed with amyloid precursor protein (APP) Tg mice to evaluate the protective effects of endogenous n-3 PUFAs on cognitive and behavioral deficits of APP Tg mice. ⋯ From the results, the expression of fat-1 transgene increased cortical n-3: n-6 PUFAs ratio and n-3 PUFAs concentrations, and sensorimotor dysfunction and cognitive deficits in AD were significantly less severe in APP/fat-1 mice with endogenous n-3 PUFAs than in APP mice controls. The protection against disturbance of spontaneous motor activity and cognitive deficits in AD was strongly correlated with increased n-3: n-6 PUFAs ratio and endogenous n-3 PUFAs, reduced APP generation, inhibited amyloid β peptide aggregation, suppressed nuclear factor-kappa B and astroglia activation, and reduced death of neurons in the cortex of APP/fat-1 mice compared with APP mice controls. In conclusion, our study demonstrates that an available medication with the maintenance of enriched n-3 PUFAs in the brain could slow down cognitive decline and prevent neuropsychological disorder in AD.
-
Spreading depression (SD), a slow propagating depolarization wave, plays an important role in pathophysiology of different neurological disorders. Yet, research into SD-related disorders has been hampered by the lack of non-invasive recording techniques of SD. Here we compared the manifestations of SD in continuous non-invasive electroencephalogram (EEG) recordings to invasive electrocorticographic (ECoG) recordings in order to obtain further insights into generator structures and electrogenic mechanisms of surface recording of SD. ⋯ Furthermore, this novel method of recording and analysis was able to separate SD recorded by scalp electrodes from non-neuronal DC shifts induced by other potential generators, such as the skin, muscles, arteries, dura, etc. These data suggest a novel application for continuous non-invasive monitoring of DC potential changes, such as SD. Non-invasive monitoring of SD would allow early intervention and improve outcome in SD-related neurological disorders.