The European journal of neuroscience
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In developing Wistar albino rats, ventral horn muscle afferent boutons are lost following corticospinal innervation. Motor cortex lesions rescue a proportion of these boutons and perturb activity dependent expression of cJun and parvalbumin (PV) in the spinal cord. Therefore, we tested whether activity-dependent competition between corticospinal and proprioreceptive afferents determines the balance of these inputs to motor output pathways by delivering the inhibitory GABA agonist muscimol unilaterally to the forelimb motor cortex using slow release polymer implants from postnatal day 7 (P7) coincident with corticospinal synaptogenesis. ⋯ In muscimol treated animals, significantly fewer neurons expressed PV in the inhibited hemicortex, but as many CTB labelled corticospinal neurons were present as in controls, along with an equally large corticospinal projection from contralateral to the implant, significantly greater than in controls. Unexpectedly, unilateral inhibition of the motor cortical input did not lead to an expanded muscle afferent input. Instead, this was reduced coincident with development of a bilateral corticospinal innervation.
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Comparative Study
Delta9-tetrahydrocannabinol decreases somatic and motivational manifestations of nicotine withdrawal in mice.
The possible interactions between Delta9-tetrahydrocannabinol (Delta9-THC) and nicotine remain unclear in spite of the current association of cannabis and tobacco in humans. The aim of the present study was to explore the interactions between these two drugs of abuse by evaluating the consequences of Delta9-THC administration on the somatic manifestations and the aversive motivational state associated with nicotine withdrawal in mice. Acute Delta9-THC administration significantly decreased the incidence of several nicotine withdrawal signs precipitated by mecamylamine or naloxone, such as wet-dog-shakes, paw tremor and scratches. ⋯ Finally, Delta9-THC also reversed conditioned place aversion associated to naloxone precipitated nicotine withdrawal. Taken together, these results indicate that Delta9-THC administration attenuated somatic signs of nicotine withdrawal and this effect was not associated with compensatory changes on CB1 cannabinoid receptors during chronic nicotine administration. In addition, Delta9-THC also ameliorated the aversive motivational consequences of nicotine withdrawal.
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Comparative Study
Altered circadian locomotor activity in APP23 mice: a model for BPSD disturbances.
Over the past decade, clinical Alzheimer's disease research has been challenged with an increased interest in noncognitive symptomatology, commonly referred to as behavioural and psychological signs and symptoms of dementia (BPSD). In accordance, major attention is being paid to behavioural alterations in the phenotyping of transgenic mouse models. Besides an age-dependent decline of cognitive functions, the APP23 model was previously shown to exhibit cage activity disturbances, reminiscent of diurnal rhythm disturbances in Alzheimer patients. ⋯ The APP23 model was therefore shown to display an age-dependent development of cage activity disturbances and sundowning-like behaviour. A comparison is made with actigraphic recordings of human Alzheimer patients exhibiting sundowning behaviour. This first report of diurnal rhythm disturbances and sundowning-like phenomena in a transgenic mouse model greatly adds to the validity of the APP23 model.
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Recent evidence suggests that spinal cord glia can contribute to enhanced nociceptive responses. However, the signals that cause glial activation are unknown. Fractalkine (CX3C ligand-1; CX3CL1) is a unique chemokine expressed on the extracellular surface of spinal neurons and spinal sensory afferents. ⋯ In addition, a single injection of fractalkine receptor antagonist (neutralizing antibody against rat CX3C receptor-1; CX3CR1) delayed the development of mechanical allodynia and/or thermal hyperalgesia in two neuropathic pain models: chronic constriction injury (CCI) and sciatic inflammatory neuropathy. Intriguingly, anti-CX3CR1 reduced nociceptive responses when administered 5-7 days after CCI, suggesting that prolonged release of fractalkine may contribute to the maintenance of neuropathic pain. Taken together, these initial investigations of spinal fractalkine effects suggest that exogenous and endogenous fractalkine are involved in spinal sensitization, including that induced by peripheral neuropathy.
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Comparative Study
NGF and GDNF differentially regulate TRPV1 expression that contributes to development of inflammatory thermal hyperalgesia.
The transient receptor potential ion channel, TRPV1 plays an essential role in the development of inflammatory thermal hyperalgesia. We investigated the dependence of inflammatory TRPV1 induction on neurotrophic factor. Rat dorsal root ganglia (DRG) neurons were classified according to immunostaining for trk-A and IB4 and the effects of antibodies against NGF or GDNF on TRPV1 expression within the groups were then analysed by immunohistochemical means. ⋯ Increased TRPV1 expression within trk-A positive neurons was prevented by anti-NGF but not by anti-GDNF, whereas TRPV1 induction within the IB4 positive group was blocked by anti-GDNF but not by anti-NGF. Both antibodies prevented the short latency of withdrawing an inflamed paw from radiant heat. These results suggest that inflammation differentially increases both NGF and GDNF, which facilitate TRPV1 expression within distinctive neurons to induce thermal hyperalgesia.