Biomedical subjects

M Zhuo

Publications and source records attributed to M Zhuo.

59 records · Page 4Linked to original sources

PubMed1989

Evidence for the involvement of a descending cholinergic pathway in systemic morphine analgesia.

The analgesic effect of morphine sulfate (3-5 mg/kg, i.p.) was assessed by both tail-flick and hot-plate tests in unanesthetized restrained rats. Intrathecal administration of atropine sulfate (10 micrograms) in the lumbar region of the spinal cord powerfully reduced the analgesia induced by systemic administration of morphine. This action did not result from the diffusion of atropine from its administration site to more rostral sites in the central nervous system. In spinal rats, atropine failed to reverse morphine analgesia, thus strongly suggesting that either a cholinergic descending pathway or a spinal local cholinergic circuit activated by an unknown descending pathway may be involved in the systemic morphine analgesia. In addition, the involvement of the alpha-adrenergic descending pathway in morphine analgesia is confirmed, whereas that of the serotonergic descending pathway is less prominent.

Analgesia↗

PubMedDate not supplied

Long-term depression: a learning-related type of synaptic plasticity in the mammalian central nervous system.

Studies of various forms of synaptic plasticity in the central nervous system have provided insights into the cellular and molecular mechanisms for certain types of learning and memory. Activity-induced decreases and increases in synaptic efficacy can be elicited in mammalian neurons. Long-term depression (LTD) and long-term potentiation (LTP) are two major forms of activity-dependent synaptic plasticity in the brain. LTD of excitatory synaptic transmission in the cerebellum in the most well studied form of synaptic depression. The induction of cerebellar LTD requires conjunctive activation of alpha-amino-3-hydroxy-5-methyl-4-isoxalepropionate (AMPA) receptors, metabotropic glutamate receptors (mGluRs) and L-type voltage-dependent Ca2+ channels. Several intracellular second messengers and protein kinases are critical for cerebellar LTD, including cGMP, cGMP-dependent protein kinase and protein kinase C (PKC). A novel intercellular messenger, nitric oxide (NO), is found in the cerebellum, is released durinng synaptic stimulation, and may contribute to cerebellar LTD. The expression of cerebellar LTD is mediated by postsynaptic desensitization of AMPA receptors. Recently, a form of homosynaptic LTD has been described in the CA1 region of the hippocampus. The induction of hippocampal LTD is postsynaptic. N-Methyl-D-aspartate receptors and mGluRs are important for induction of hippocampal LTD. Other intracellular and intercellular messengers, such as NO, cGMP and cAMP, might act downstream from glutamate receptors during hippocampal LTD. The expression of hippocampal LTD is likely to be in part presynaptic. While cerebellar LTD may be important for motor learning, the behavioral role of hippocampal LTD remains to be explored.

Animals↗

PubMedDate not supplied

On the respective roles of nitric oxide and carbon monoxide in long-term potentiation in the hippocampus.

Perfusion of hippocampal slices with an inhibitor nitric oxide (NO) synthase blocked induction of long-term potentiation (LTP) produced by a one-train tetanus and significantly reduced LTP by a two-train tetanus, but only slightly reduced LTP by a four-train tetanus. Inhibitors of heme oxygenase, the synthetic enzyme for carbon monoxide (CO), significantly reduced LTP by either a two-train or four-train tetanus. These results suggest that NO and CO are both involved in LTP but may play somewhat different roles. One possibility is that NO serves a phasic, signaling role, whereas CO provides tonic, background stimulation. Another possibility is that NO and CO are phasically activated under somewhat different circumstances, perhaps involving different receptors and second messengers. Because NO is known to be activated by stimulation of NMDA receptors during tetanus, we investigated the possibility that CO might be activated by stimulation of metabotropic glutamate receptors (mGluRs). Consistent with this idea, long-lasting potentiation by the mGluR agonist tACPD was blocked by inhibitors of heme oxygenase but not NO synthase. Potentiation by tACPD was also blocked by inhibitors of soluble guanylyl cyclase (a target of both NO and CO) or cGMP-dependent protein kinase, and guanylyl cyclase was activated by tACPD in hippocampal slices. However, biochemical assays indicate that whereas heme oxygenase is constitutively active in hippocampus, it does not appear to be stimulated by either tetanus or tACPD. These results are most consistent with the possibility that constitutive (tonic) rather than stimulated (phasic) heme oxygenase activity is necessary for potentiation by tetanus or tACPD, and suggest that mGluR activation stimulates guanylyl cyclase phasically through some other pathway.

Animals↗

PubMedDate not supplied

The specific role of cGMP in hippocampal LTP.

Previous results have suggested that cGMP is involved in hippocampal long-term potentiation (LTP), perhaps as the presynaptic effector of a retrograde messenger. However, other studies have failed to replicate some of those results, making the role of cGMP uncertain. We therefore reexamined this question and identified several variables that can affect the contribution of cGMP. First, brief perfusion with 8-Br-cGMP before weak tetanic stimulation produced long-lasting potentiation in the CA1 region of hippocampal slices, but more prolonged perfusion with 8-Br-cGMP before the tetanus did not produce long-lasting potentiation. Second, the activity-dependent long-lasting potentiation by cGMP analogs was reduced when NMDA receptors were completely blocked, indicating that NMDA receptor activation contributes to, but is not required for, the potentiation. The amount of reduction of the potentiation differed with different protocols, and in some cases could be complete. Third, LTP produced by strong tetanic stimulation in the stratum radiatum of CA1 (which expresses eNOS) was blocked by inhibitors of soluble guanylyl cyclase or cGMP-dependent protein kinase, but LTP in the stratum oriens (which does not express eNOS) was not. The results of these experiments should help to explain some of the discrepant findings from previous studies, and, in addition, may provide insights into the mechanisms and functional role of the cGMP-dependent component of LTP.

Animals↗

PubMedDate not supplied

On the respective roles of nitric oxide and carbon monoxide in long-term potentiation in the hippocampus.

Perfusion of hippocampal slices with an inhibitor of nitric oxide (NO) synthase-blocked induction of long-term potentiation (LTP) produced by a one-train tetanus and significantly reduced LTP by a two-train tetanus, but only slightly reduced LTP by a four-train tetanus. Inhibitors of heme oxygenase, the synthetic enzyme for carbon monoxide (CO), significantly reduced LTP by either a two-train or four-train tetanus. These results suggest that NO and CO are both involved in LTP but may play somewhat different roles. One possibility is that NO serves a phasic, signaling role, whereas CO provides tonic, background stimulation. Another possibility is that NO and CO are phasically activated under somewhat different circumstances, perhaps involving different receptors and second messengers. Because NO is known to be activated by stimulation of NMDA receptors during tetanus, we investigated the possibility that CO might be activated by stimulation of metabotropic glutamate receptors (mGluRs). Consistent with this idea, long-lasting potentiation by the mGluR agonist tACPD was blocked by inhibitors of heme oxygenase but not NO synthase. Potentiation by tACPD was also blocked by inhibitors of soluble guanylyl cyclase (a target of both NO and CO) or cGMP-dependent protein kinase, and guanylyl cyclase was activated by tACPD in hippocampal slices. However, biochemical assays indicate that whereas heme oxygenase is constitutively active in hippocampus, it does not appear to be stimulated by either tetanus or tACPD. These results are most consistent with the possibility that constitutive (tonic) rather than stimulated (phasic) heme oxygenase activity is necessary for potentiation by tetanus or tACPD, and suggest that mGluR activation stimulates guanylyl cyclase phasically through some other pathway.

Animals↗