Neuroscience
-
Nicotinic acetylcholine receptors (nAChRs) produce widespread and complex effects on neocortex excitability. We studied how heteromeric nAChRs regulate inhibitory post-synaptic currents (IPSCs), in fast-spiking (FS) layer V neurons of the mouse frontal area 2 (Fr2). In the presence of blockers of ionotropic glutamate receptors, tonic application of 10μM nicotine augmented the spontaneous IPSC frequency, with minor alterations of amplitudes and kinetics. ⋯ We conclude that α4β2∗ nAChRs can produce sustained regulation of FS cells in Fr2 layer V. The effect presents a presynaptic component, whereas the somatic regulation decreases with age. These mechanisms may contribute to the nAChR-dependent stimulation of excitability during cognitive tasks as well as to the hyperexcitability caused by hyperfunctional heteromeric nAChRs in sleep-related epilepsy.
-
A single exposure to amphetamine induces neurochemical sensitization in striatal areas. The neuropeptide angiotensin II, through AT1 receptors (AT1-R) activation, is involved in these responses. However, amphetamine-induced alterations can be extended to extra-striatal areas involved in blood pressure control and their physiological outcomes. ⋯ Meanwhile, no differences were found neither in CeAmy nor A1. Sensitized blood pressure response was observed as sustained changes in mean arterial pressure and was effectively prevented by AT1-R blockade. Our results extend AT1-R role in amphetamine-induced sensitization over noradrenergic nuclei and their cardiovascular output.
-
Although it is still debated whether vasoconstriction underlies migraine resolution by triptans, they are not recommended in patients at cardiovascular risk. However, relationship between stroke incidence and triptan use is unclear, and it is unknown whether acute or chronic use of these drugs worsens ischemic brain injury. To address this issue, we investigated the effect of clinically-relevant doses of the potent cerebral artery vasoconstrictor eletriptan on cerebral blood flow (CBF) and brain infarct volumes, as well as on expression of genes involved in cerebrovascular regulation. ⋯ Finally, chronic eletriptan reduced brain mRNAs for PACAP and VIP, leaving unaffected those for 5HT1B/DR and CGRP. No significant transcript changes were found in dura mater. Data suggest that the impact of triptans on cerebral hemodynamic should be re-evaluated, as well as their propensity to increase stroke risk in migraineurs.
-
Every spring, deer cast their old antlers and initiate a regeneration process, which yields a new set of antlers of up to 1m in length. Over the course of three months, branches of the trigeminal nerve, originating from the frontal skull, innervate velvet, a modified skin that covers the regenerating antler. The rate of growth of these axons reaches up to 2cm per day making them the fastest regenerating axons in adult mammals. ⋯ Our proteomic analyses identified several axon growth promoters in the velvet-conditioned medium (VCM), including soluble proteins such as nerve growth factor (NGF) and apolipoprotein A-1, as well as matrix extracellular proteins, such as periostin and SPARC. Additional in vitro analyses allowed us to determine that a synergic relationship between periostin and NGF may contribute to neurite growth-promoting effects of velvet secretome. A combinatorial approach using these factors may promote regeneration at high speeds in patients with peripheral neuropathies.
-
The M-current (IM) is a voltage-dependent, persistent K+ current so termed because it is strongly inhibited by the cholinergic agonist muscarine. The IM main function is to limit neuronal excitability by contrasting action potential firing. Although motoneurons are sensitive to acetylcholine, the role of IM in modulating their excitability is still controversial. ⋯ Current-clamp experiments demonstrated that IM strongly regulated HM action potential firing, since both muscarine and linopirdine increased spike frequency whereas the M-channel opener retigabine (20μM) reduced it. Conversely, IM seemed uninvolved in the generation of the medium afterhyperpolarizing potential. Our results suggest that HMs possess IM, whose pharmacological modulation is an important tool to up- or down-regulate excitability, to be explored in experimental models of neurodegeneration.