Neuroscience
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Cyclooxygenase-2 (COX-2) after induction peripherally, and within the CNS, plays an important role in producing inflammatory pain. However, its role in neuropathic pain models is controversial. Recently a robust and persistent model of partial nerve injury pain, the spared nerve injury (SNI) model, has been developed. ⋯ Furthermore, rofecoxib treatment (1 and 3.2 mg/kg for 5 and 3 days respectively starting on the day of surgery) failed to modify the development of allodynia and hyperalgesia in the SNI model. However, rofecoxib significantly reduced inflammatory hypersensitivity evoked by injection of complete Freund's adjuvant into one hindpaw, indicating that the doses used were pharmacologically active. The pain hypersensitivity produced by the SNI model is not COX-2-dependent.
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Comparative Study
M2 muscarinic receptors in pontine reticular formation of C57BL/6J mouse contribute to rapid eye movement sleep generation.
Microinjecting the acetylcholinesterase inhibitor neostigmine into the pontine reticular formation of C57BL/6J (B6) mouse causes a rapid eye movement (REM) sleep-like state. This finding is consistent with similar studies in cat and both sets of data indicate that the REM sleep-like state is caused by increasing levels of endogenous acetylcholine (ACh). Muscarinic cholinergic receptors have been localized to the pontine reticular formation of B6 mouse but no previous studies have examined which of the five muscarinic receptor subtypes participate in cholinergic REM sleep enhancement. ⋯ Pertussis toxin and methoctramine significantly decreased the neostigmine-induced REM sleep-like state. In contrast, pretreatment with pirenzepine did not significantly decrease the REM sleep-like state caused by neostigmine. These results support the interpretation that M2 receptors in the pontine reticular formation of B6 mouse contribute to the generation of REM sleep.
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A diet high in total fat (HF) reduces hippocampal levels of brain-derived neurotrophic factor (BDNF), a crucial modulator of synaptic plasticity, and a predictor of learning efficacy. We have evaluated the capacity of voluntary exercise to interact with the effects of diet at the molecular level. Animal groups were exposed to the HF diet for 2 months with and without access to voluntary wheel running. ⋯ Results indicate that exercise interacts with the same molecular systems disrupted by the HF diet, reversing their effects on neural function. Reactive oxygen species, and BDNF in conjunction with its downstream effectors on synaptic and neuronal plasticity, are common molecular targets for the action of the diet and exercise. Results unveil a possible molecular mechanism by which lifestyle factors can interact at a molecular level, and provide information for potential therapeutic applications to decrease the risk imposed by certain lifestyles.
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Comparative Study
Modulation of activator protein 1/DNA binding activity by acoustic overstimulation in the guinea-pig cochlea.
Changes in gene expression are part of the homeostatic machinery with which cells respond to external stimuli or assaults. The activity of the early response transcriptional factor activator protein-1 (AP-1) can be modulated by a variety of environmental stimuli including those that alter the cellular oxidation/reduction status. This study investigates the activation of AP-1/DNA binding in the guinea-pig cochlea in response to acoustic overstimulation which produces reactive oxygen species. ⋯ Incubation of nuclear extracts with antibodies against Fos/Jun family proteins prior to a supershift assay showed Fra-2 as a major component of the AP-1 complex immediately after the noise exposure. In the organ of Corti, Fra-2 immunoreactivity was localized to the middle turn, i.e. the region which is most affected by the 4-kHz octave band exposure. The results suggest the modulation of gene expression via the activation of AP-1 as a consequence of noise trauma but also demonstrate differential responses in cochlear tissues.
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Comparative Study
Developmental expression of methyl-CpG binding protein 2 is dynamically regulated in the rodent brain.
The gene encoding methyl-CpG binding protein 2 (MeCP2) is mutated in the large majority of girls that have Rett Syndrome (RTT), an X-linked neurodevelopmental disorder. To better understand the developmental role of MeCP2, we studied the ontogeny of MeCP2 expression in rat brain using MeCP2 immunostaining and Western blots. MeCP2 positive neurons were present throughout the brain at all ages examined, although expression varied by region and age. ⋯ The timing of MeCP2 expression in the granule cell layer is coincident with the onset of granule cell synapse formation. Although more subtle, the degree of MeCP2 expression in cortex and hippocampus was most closely correlated with synaptogenesis in both regions. Our finding that MeCP2 expression is correlated with synaptogenesis is consistent with the hypothesis that Rett Syndrome is caused by defects in the formation or maintenance of synapses.