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Biomedical subjects

D A Carter

Publications and source records attributed to D A Carter.

At least 109 records · Page 6Linked to original sources
PubMed1990

Regrowth and connectivity of injured central nervous system axons in adult rodents.

The capacity of injured nerve cells to regrow and form terminal connections in the CNS of adult mammals was investigated in axotomized retinal ganglion cells (RGCs) of rodents whose optic nerves were substituted by an autologous segment of peripheral nerve. While many RGCs died after axotomy approximately 20% of the surviving RGCs regenerated axons several cm in length. Some of the regenerated RGC axons entered the superior colliculus where they arborized and formed well differentiated synapses that transynaptically excited or inhibited tectal neurons.

Animals↗
PubMed1989

Electrophysiologic responses in hamster superior colliculus evoked by regenerating retinal axons.

Autologous peripheral nerve grafts were used to permit and direct the regrowth of retinal ganglion cell axons from the eye to the ipsilateral superior colliculus of adult hamsters in which the optic nerves had been transected within the orbit. Extracellular recordings in the superior colliculus 15 to 18 weeks after graft insertion revealed excitatory and inhibitory postsynaptic responses to visual stimulation. The finding of light-induced responses in neurons in the superficial layers of the superior colliculus close to the graft indicates that axons regenerating from axotomized retinal ganglion cells can establish electrophysiologically functional synapses with neurons in the superior colliculus of these adult mammals.

Action Potentials↗
PubMed1989

Cyclic nucleotide dynamics in the rat hypothalamus during osmotic stimulation: in vivo and in vitro studies.

The molecular mechanisms which regulate expression of vasopressin (AVP)- and oxytocin (OT)-encoding genes are unknown. We have investigated the regulatory role of one class of second messenger, the cyclic nucleotides, by examining levels of both adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) in hypothalamic nuclei of rats during osmotic stimulation. In vivo studies, in which rats were given 2% saline to drink for different periods (salt loading), demonstrated elevated levels of cAMP in the supraoptic nucleus (SON) after 2 days. Raised levels were also evident at 3 and 7 days. A similar (less marked) pattern was observed in the paraventricular nucleus (PVN) but not in the suprachiasmatic nucleus (SCN). cGMP was present at much lower levels than cAMP and did not exhibit parallel dynamics during salt loading; however, significant changes in cGMP levels were found in the SON and PVN. In vitro studies, in which explant cultures of punched hypothalamic nuclei were challenged with hypertonic media, demonstrated that increasing medium osmolality from 290 to 310 mOsm/kg doubled the level of cAMP in the SON but did not change levels in the PVN or SCN. A greater stimulus, 325 mOsm/kg, caused a 4-fold increase in SON cAMP, and small cAMP responses in the PVN and SCN. Marked cGMP responses were also observed in the SON following stimulation at 310 and 325 mOsm/kg, smaller responses being found in the PVN and SCN. These results are consistent with previous demonstrations of SON neuron osmosensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Independent regulation of neuropeptide mRNA level and poly(A) tail length.

Osmotic stimulation increases arginine-vasopressin (AVP) and oxytocin (OT) mRNA levels and poly(A) tail size concurrently. We now show that these changes are independently regulated. Whereas depletion of serotonin with p-chlorophenylalanine (PCPA) blocked the increase in hypothalamic levels of AVP and OT mRNA following osmotic stimuli in rats (2% saline drinking or dehydration), the increase in mRNA size was similar in PCPA and control animals. PCPA alone did not modify mRNA size. In addition to demonstrating an apparent obligatory role for serotonin in osmotically induced AVP and OT mRNA accumulation, the results provide evidence for different signaling pathways mediating transcript abundance and poly(A) tail length. Direct investigation of the regulatory mechanisms should be amenable to study in this system.

Animals↗
PubMed1989

Diurnal rhythm of vasopressin mRNA species in the rat suprachiasmatic nucleus: independence of neuroendocrine modulation and maintenance in explant culture.

Vasopressin mRNA in the suprachiasmatic nucleus (SCN) of the rat brain exhibits diurnal variation in poly(A) tail length; a single species of mRNA identical in size to that in other hypothalamic nuclei is expressed in the light phase of the daily cycle whereas a second, smaller species is expressed in the dark phase. We have investigated the neuroendocrine factors which may regulate this rhythm by comparing vasopressin mRNA size with Northern analysis of RNA extracted from SCN tissue taken at 09.00 h (light phase) and 21.00 h (dark phase). The consistent rhythmic variation observed in normal male rats was not modified in either adrenalectomized or castrated animals or in ovariectomized female rats. The rhythm was also not disrupted following treatment with the serotonin-depleting agent parachlorophenylalanine, or following treatment with either melatonin or the benzodiazepine, triazolam. We next investigated whether the daily pattern of expression was maintained in isolated SCN. Microdissected blocks containing the paired SCN were explanted into culture at various times of the day for a period of 4 h. Vasopressin mRNA extracted from light phase cultures (11.00-15.00 h) exhibited no size change from control SCN mRNA taken at either 11.00 h or 15.00 h. In contrast, mRNA from cultures maintained over the period 16.00-20.00 h (lights off: 18.00 h) exhibited a marked size difference from 16.00 h controls, being similar to the smaller species observed in 20.00 h controls. Similarly, vasopressin mRNA from cultures maintained over the period 05.00-09.00 h (lights on 06.00 h) was similar in size to 09.00 h controls and contrasted to the pattern of expression observed in 05.00 h controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1989

gamma-Aminobutyric acid regulation of neurohypophysial hormone secretion in male and female rats.

The role of gamma-aminobutyric acid (GABA) in the control of oxytocin and arginine vasopressin (AVP) release from the posterior pituitary was investigated using the GABA agonist muscimol and the GABA antagonists bicuculline and picrotoxin. Two perifusion model systems were studied using (a) intact isolated posterior pituitaries (IPP) and (b) neurosecretosomes from both male and female rats. In experiments on tissue from male rats, the stimulated release of oxytocin and AVP in both models was inhibited by muscimol, an effect which was reversed in the presence of bicuculline. Bicuculline alone increased the release of oxytocin only. Although similar responses to muscimol or bicuculline were seen in neurosecretosomes from female animals, neither agent affected oxytocin and AVP release from the intact IPP. Picrotoxin had a similar effect to bicuculline on oxytocin in isolated posterior pituitaries from male as well as female rats, although at the neurosecretosome level a paradoxical inhibition was observed. These results provide evidence for an endogenous GABA receptor mechanism at the level of the neurosecretory terminals in both male and female rats. The sexually dimorphic IPP response suggests a second more complex mechanism involving either pituicytenerve terminal interactions and/or a secondary role of other neurotransmitters in the GABA regulation of neurohypophysial hormones.

Animals↗
PubMed1989

Regenerated retinal ganglion cell axons can form well-differentiated synapses in the superior colliculus of adult hamsters.

To investigate in adult animals the distribution and differentiation of the synapses made by axotomized CNS neurons whose regenerating axons are guided back to their natural targets in the brain, we attached an autologous peripheral nerve (PN) graft 2-3 cm in length to the ocular stump of a transected optic nerve (ON) in adult hamsters, inserted the distal end of the graft into the superior colliculus (SC), and, 6-8 weeks later, labeled the retinal ganglion cell (RGC) axons that entered the SC with HRP orthogradely transported from the eye. By light microscopy, regenerated RGC axons extended from the graft into the retinorecipient layers of the SC for up to 500 microns, distances that approximate the lengths of normal RGC arbors. We compared 698 control and 758 regenerated HRP-labeled axon terminals from 4 intact and 4 experimental animals by electron microscopy. The structure of the regenerated RGC terminals, the type of synaptic contacts formed, the ratios of contacts to terminal perimeter, and the domains of the postsynaptic neurons contacted were similar to those of controls. These results indicate that regenerated RGC axons can form well-differentiated synapses in the SC. Morphological differences between the regenerated and control synapses were the larger size of some regenerated terminals, the greater mean length of the regenerated synapses, and the higher proportion of contacts with dendrites that contained vesicles. The synaptic differentiation attained by these reformed retinocollicular projections suggests that regenerating CNS axons and their target neurons in the adult mammalian brain may retain or reexpress certain molecular determinants of normal connectivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Sexual differentiation of oxytocin stress responsiveness: effect of neonatal androgenization, castration and a luteinizing hormone-releasing hormone antagonist.

The plasma OT increment following stress in rats is sexually dimorphic, females exhibiting greater responses than males. We have investigated the role of neonatal androgen secretion in determining the sex-typical level of response. Castration of male pups either surgically or functionally (GnRH antagonist treatment) within either 2 h or 5 days of birth did not elevate the OT responses of adult males. In contrast, androgenization of female pups (testosterone, 1.25 mg/pup) within 5 days of birth markedly reduced the OT stress responses of adults to a level insignificantly different to males. The results show that neonatal androgens can exert organizational effects on OT regulatory mechanisms. Since neonatal castration was ineffective it would appear that a prenatal defeminization or masculinization event determines OT stress responsiveness in males.

Animals↗
PubMed1987

A role for the area postrema in mediating cholecystokinin-stimulated oxytocin secretion.

We have investigated the role of the area postrema (AP) in mediating the neurohypophyseal hormone response to peripheral administration of nausea-producing agents in rats. In control animals, lithium chloride (LiCl) and apomorphine (APO) caused a rise in plasma levels of immunoreactive oxytocin (OT) and arginine-vasopressin (AVP), whereas sulphated cholecystokinin octapeptide (CCK-8s) stimulated OT secretion only. Rats with AP lesions exhibited a similar OT and AVP response to LiCl and APO but the OT response to CCK-8s was significantly diminished. The results indicate that the selective stimulation of OT secretion by CCK-8s is partly mediated via the AP. Although the nausea-producing effects of LiCl and APO may involve the AP, the neuroendocrine effects of these agents may well be mediated via actions outside the AP.

Animals↗
PubMed1987

Temporal changes in the activity of endogenous opioid mechanisms regulating oxytocin secretion in saline-loaded rats.

The effect of the opiate antagonist naloxone on neurohypophyseal hormone secretion has been investigated in rats given 2% NaCl to drink for 0-9 days. Naloxone elicited a rise in plasma levels of oxytocin (OT), but not arginine-vasopressin (AVP), on days 1-3 only, the greatest response being on day 2. In a further experiment, the OT response to an acute stimulus (1.5 M NaCl, i.p.) was found to be similar in controls and rats drinking 2% NaCl for 7 days, indicating that depletion of readily releasable hormone was not the cause of the loss of sensitivity to naloxone; rather a down-regulation of opiate receptor mechanisms may be responsible. The temporal changes in opiate antagonist-sensitivity in saline-loaded rats may provide a functional paradigm for the investigation of regulatory opiate mechanisms in neural tissue.

Animals↗
PubMed1987

Opioid control of oxytocin secretion: evidence of distinct regulatory actions of two opiate receptor types.

Stress induced oxytocin (OT) secretion was measured in female rats following treatment with various opiate antagonists selective for different types of opiate receptor. Naloxone (mu selective) and MR2266 BS (kappa selective) potentiated the OT response to an emotional stress (1 min. immobilization) whereas the delta selective antagonist ICI 154129 was without effect. Similarly, naloxone and MR2266 BS, but not ICI 154129, potentiated the response to a physical stress (i.p. hypertonic saline). A dose response comparison of the actions of naloxone and MR2266 BS revealed that naloxone was most effective in potentiating the immobilization response whereas MR2266 BS elicited greater responses than naloxone when administered prior to hypertonic saline. The results indicate that the opioid regulation of stress induced OT secretion is primarily mediated via mu and kappa opiate receptor types, the two types differentially regulating the OT response to two different stressors.

Animals↗
PubMed1987

Modulation of oxytocin secretion by ascending noradrenergic pathways: sexual dimorphism in rats.

We have investigated the role of ascending noradrenergic pathways in the control of oxytocin (OT) and arginine-vasopressin (AVP) secretion during acute immobilization stress in male and female rats. 6-Hydroxydopamine-induced lesions of the ventral noradrenergic bundle (VNAB) resulted in a selective depletion of hypothalamic noradrenaline content. In sham-lesioned rats plasma levels of OT were raised following stress, the response being significantly greater in female compared with male animals. VNAB lesions were not associated with altered responses in female rats, whereas lesioned males exhibited markedly elevated OT stress responses. AVP secretion was not modulated in VNAB-lesioned rats of either sex. The results provide functional evidence of a sexually dimorphic inhibitory role of the VNAB in the control of OT secretion.

Afferent Pathways↗
PubMed1987

Neuropeptide Y alters monoamine turnover in the rat brain.

The effects of intracerebroventricular administration of neuropeptide Y (NPY) on central monoamine turnover were studied in rats treated with alpha-methyl-p-tyrosine (alpha-MPT). NPY decreased noradrenaline turnover in the brainstem, hypothalamus, midbrain and hippocampus. Dopamine turnover was decreased in the brainstem and striatum of NPY-treated rats. Although alpha-MPT did not seem to affect the turnover of serotonin, the concentration of this amine after the administration of NPY was higher in the brainstem, hypothalamus and striatum. Our results suggest that NPY may play a role in the modulation of monoamine turnover in the central nervous system.

Animals↗
PubMed1987

Selective mediation of kappa-opioid central cardiovascular effects by ascending noradrenergic pathways.

The role of ascending noradrenergic pathways in the mediation of central opiate-induced cardiovascular effects has been investigated. The effects of selective kappa- and delta-opiate agonists microinjected into the nucleus tractus solitarius (NTS) of urethane anaesthetized rats were compared following 6-hydroxydopamine lesions of either the dorsal (DNAB) or ventral (VNAB) noradrenergic bundles. In sham lesioned animals both opiates elicited a significant pressor effect and a variable but consistent bradycardia. The delta-agonist responses were not modified in lesioned rats. In marked contrast the pressor effect of the kappa-agonist was abolished in both DNAB and VNAB lesioned rats. The bradycardic response was not significantly modified. These findings are consistent with previous observations that the cardiovascular effects of kappa- and delta-opiates in the NTS are mediated via different mechanisms, and provide evidence for selective functional actions of endogenous opioids within brain nuclei.

Afferent Pathways↗
PubMed1987

The numbers of unmyelinated and myelinated axons in normal and regenerated rat saphenous nerves.

Counts have been made of the numbers of unmyelinated and myelinated axons in the proximal and distal stumps of regenerated rat saphenous nerves and from equivalent sites in normal nerves. In the proximal part of normal nerves there were averages of 1,045 myelinated axons and 4,160 unmyelinated ones. Regenerated nerves contained the same number of myelinated axons in their proximal stumps but there was a 40% reduction in the unmyelinated axon count. In the distal stumps of these nerves the myelinated axon count had increased by an average of 620; this comes about because some regenerated myelinated axons support more than one process in the distal stump. In contrast, the number of unmyelinated axons was reduced further, from a mean of 2,476 in the proximal stump to one of 2,219. The sizes of Schwann cell units in the normal and regenerated nerves were also noted. Schwann cell units in the proximal and distal stumps of the regenerated nerves were smaller than those in the normal ones. These changes associated with unmyelinated axons in regenerated nerves are likely to contribute to the sensory, vasomotor and sudomotor abnormalities that sometimes occur after peripheral nerve injury and regeneration.

Animals↗
PubMed1987

Oxytocin stress responses are dependent upon emotionality.

Comparison of posterior pituitary responses to stress in rat strains with contrasting emotionality has revealed an inverse relationship between oxytocin (OT) responses and emotional reactivity. The plasma OT and arginine-vasopressin (AVP) responses to stress were determined in two psychogenetically selected strains of rat, Roman high avoidance (RHA) and Roman low avoidance (RLA), RLA's being more emotionally reactive than RHA's. Following 1 min immobilisation stress, plasma levels of OT were significantly higher in RHA's compared to RLA's. This finding correlates with the previous demonstration of a sex difference in the OT stress response, females having a higher response than males. Plasma levels of AVP were not significantly modified by immobilization in either strain of rat. However, control levels of AVP were markedly raised in both male and female RHA's.

Arginine Vasopressin↗