Neuroscience letters
-
Neuroscience letters · Mar 2013
COMT and MTHFR polymorphisms interaction on cognition in schizophrenia: an exploratory study.
The investigation of the catechol-O-methyltransferase (COMT-[rs4680]) and methylenetetrahydrofolate reductase (MTHFR-[rs1801133]) polymorphisms' interaction might shed light into the pathogenetic mechanisms of the cognitive dysfunction in schizophrenia. In an exploratory study, we hypothesized that the MTHFR 677T allele which has been related to a hypoactive MTHFR enzyme would augment the unfavorable effects of COMT Val158 homozygosity which has been associated with COMT enzyme hyperfunction. 90 schizophrenia patients and 55 healthy volunteers were assessed on psychomotor speed, pattern and spatial recognition memory (SRM), spatial working memory (SWM), attentional flexibility and planning (Stockings of Cambridge-SOC). IQ scores in a random subgroup of patients were also measured. ⋯ In conclusion, COMT and MTHFR polymorphisms interacted on cognition, suggesting that the MTHFR enzyme activity might moderate the effects of the COMT enzyme. In contrast to our initial hypothesis, the MTHFR T-allele attenuated the cognitive effects of COMT Val homozygosity. In this preliminary study, we propose that dopaminergic and intracellular methylation mechanisms could interact on cognitive deficits in schizophrenia.
-
Previous imaging studies have described gray and white matter alterations in the cerebellum, the posterior aspects of the visual system and in the corpus callosum in patients with schizophrenia. Here, we investigated these regions in more detail using tract-based spatial statistics (TBSS). Additionally, we evaluated potential changes in lateralization of the optic radiation and the superior cerebellar peduncle. ⋯ Our findings substantiate the concept that schizophrenia is a neurodevelopmental disorder and indicate that changes in lateralization may play a key role in the pathogenesis of this disease.
-
Neuroscience letters · Mar 2013
Comparative StudyVoluntary resistance running induces increased hippocampal neurogenesis in rats comparable to load-free running.
Recently, we reported that voluntary resistance wheel running with a resistance of 30% of body weight (RWR), which produces shorter distances but higher work levels, enhances spatial memory associated with hippocampal brain-derived neurotrophic factor (BDNF) signaling compared to wheel running without a load (WR) [17]. We thus hypothesized that RWR promotes adult hippocampal neurogenesis (AHN) as a neuronal substrate underlying this memory improvement. Here we used 10-week-old male Wistar rats divided randomly into sedentary (Sed), WR, and RWR groups. ⋯ We found that even when the average running distance decreased by about half, the average work levels significantly increased in the RWR group, which caused muscular adaptation (oxidative capacity) for fast-twitch plantaris muscle without causing any negative stress effects. Additionally, immunohistochemistry revealed that the total BrdU-positive cells and newborn mature cells (BrdU/NeuN double-positive) in the dentate gyrus increased in both the WR and RWR groups. These results provide new evidence that RWR has beneficial effects on AHN comparable to WR, even with short running distances.
-
Neuroscience letters · Mar 2013
Signal flow and pathways in response to early Wallerian degeneration after rat sciatic nerve injury.
Wallerian degeneration (WD) remains a subject of critical research interest in modern neurobiology. WD is a process which a large number of genes are differentially regulated, especially the early response to activate nerve degeneration and regeneration, but the precise mechanisms remain elusive. ⋯ KEGG pathway analysis revealed activity mainly relating to cytokine-cytokine receptor interaction, MAPK signaling pathway, Jak-STAT signaling pathway, ErbB signaling pathway and TGF-beta signaling pathway involved in the recurrent neural networks that were regulated by the key factors, Cldn-14, Cldn-15, ITG, BID and BIRC3. These results will help to much better understand information relating to the early response to WD and provide us with a firmer basis in future investigations on the molecular mechanisms of WD that regulate nerve degeneration and/or regeneration.
-
Neuroscience letters · Mar 2013
Antinociception by systemically-administered acetaminophen (paracetamol) involves spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral adenosine A1 receptors.
Acetaminophen (paracetamol) is a widely used analgesic, but its sites and mechanisms of action remain incompletely understood. Recent studies have separately implicated spinal adenosine A(1) receptors (A(1)Rs) and serotonin 5-HT(7) receptors (5-HT(7)Rs) in the antinociceptive effects of systemically administered acetaminophen. In the present study, we determined whether these two actions are linked by delivering a selective 5-HT(7)R antagonist to the spinal cord of mice and examining nociception using the formalin 2% model. ⋯ DPCPX in normal mice; this was also observed in A(1)R wild type mice, but not in those lacking A(1)Rs. In summary, we demonstrate a link between spinal 5-HT(7)Rs and A(1)Rs in the spinal cord relevant to antinociception by systemic acetaminophen. Furthermore, we implicate peripheral A(1)Rs in the antinociceptive effects of locally- and systemically-administered acetaminophen.