Wise Young
05-11-2003, 09:13 AM
• Podda MV, Deriu F, Giaconi E, Milia M and Tolu E (2003). Melatonin inhibits rat medial vestibular nucleus neuron activity in vitro. Neurosci Lett 341:209-12. Summary: The present study evaluated the effects of melatonin on the discharge rate of tonically active medial vestibular nucleus (MVN) neurons in an in vitro slice preparation of the rat dorsal brainstem. The results demonstrated that, when melatonin was applied to the slice for a period of 7-10 min, a decrease in MVN neuron firing rate was observed in 21/58 (36%) of the cells sampled. The inhibitory effects of melatonin were present in synaptic uncoupling condition and were mimicked by 2-iodomelatonin, a non-selective agonist with high affinity for melatonin membrane receptor subtypes (MT(1), MT(2), MT(3)). The MT(2) receptor antagonists luzindole and 4-phenyl-2-propionamidotetraline and the MT(3) receptor antagonist prazosin did not, however, antagonise the inhibitory effects of melatonin, indicating that melatonin may act on MVN neurons through an MT(1) receptor-mediated mechanism. Department of Biomedical Sciences (Human Physiology and Bioengineering), University of Sassari, V.le S. Pietro 43/B, I-07100, Sassari, Italy
• Pompeiano O, Manzoni D and Miele F (2002). Pineal gland hormone and idiopathic scoliosis: possible effect of melatonin on sleep-related postural mechanisms. Arch Ital Biol 140:129-58. Summary: Experimental and clinical evidences indicate that endocrine mechanisms, particularly involving the pineal gland, exert a role in the development of postural deficits leading to the occurrence of idiopatic scoliosis (IS). In particular, experiments performed in bipedal animals have shown that removal of the pineal gland, which secretes melatonin (M), induced a scoliosis, and that in such preparations, administration of this hormone prevented the development of this deformity (cf. 131). It appears also that adolescents with IS showed a reduced level of serum M with respect to age-related control subjects. The possible mechanisms involved in the M regulation of the tonic contraction of the axial musculature have been discussed. It is known that the pineal gland is implicated in the control of circadian rhythms, including the sleep-waking cycle, and that during this cycle there are prominent changes in postural activity, which affect not only the limbs, but also the axial musculature. These changes are characterized by a decrease followed by a suppression of postural activity, which occur particularly during transition from wakefulness to synchronized sleep and, more prominently, to rapid eye movement (REM) sleep. Episodes of postural atonia may also occur during the cataplectic episodes, which are typical of narcolepsy. Cholinergic and/or cholinoceptive neurons located in the dorsal pontine reticular formation (pRF) and the related medullary inhibitory reticulospinal (RS) system, intervene in the suppression of posture during REM sleep, as well as during the cataplectic episodes which occur in narcolepsy. These structures are under the modulatory (inhibitory) influence of the dorsomedial and the dorsolateral pontine tegmentum, where serotoninergic raphe nuclei (RN) neurons and noradrenergic locus coeruleus (LC) neurons are located. We postulated that M may act not only on the circadian pacemaker, but also directly on the pontine tegmental structures involved in the regulation of posture during the animal states indicated above. This hypothesis is supported by the facts that: 1) the dorsal pRF may contain specific binding sites for M; 2) this structure is particularly sensitive to M in adolescents, as well as in adult subjects affected by narcoleptic disturbances leading to cataplexy; 3) M increases the release of serotonin (5-HT), a neurotransmitter which enhances the postural tone by acting on the dorsal pRF: on the other hand, deficits in M levels may lower the activity of the serotoninergic raphe system, thus leading to a decrease or suppression of postural activity similar to that occurring either during REM sleep or during the cataplectic episodes typical of narcoleptic patients; 4) IS patients may show episodes of sleep apnea, a phenomenon which has been attibuted to a reduced tonic contraction of primary and accessory respiratory muscles during REM, resulting from a reduced release of 5-HT at dorsal pontine level. It has been postulated that, if the reduced M and 5-HT levels are subliminal to produce a complete suppression of posture under the conditions reported above, the reduced postural tone, which results from this condition may lead to the development of IS, due to hypotonia which affects the axial musculature. M secretion could be regulated not only by the activity of the serotoninergic raphe neurons projecting to the pineal gland, but probably also by the activity of noradrenergic LC neurons. It is likely that the development of IS, which results from a reduced level of M and 5-HT, may occur provided that the noradrenergic LC inhibition of the pontine structures is impaired. Such impairment could depend upon genetic factors, similar to those postulated to play a role in narcolepsy. In conclusion, the possibility exists that an impaired activity of brain monoaminergic systems may lead to disfunction in the production of M, which is apparently an important factor in the etiopathogenesis of IS. Dipartimento di Fisiologia e Biochimica, Universita di Pisa, Via S. Zeno 31, 1-56127 Pisa, Italy. pompeiano@dfb.unipi.it
• Venero JL, Absi el H, Cano J and Machado A (2002). Melatonin induces tyrosine hydroxylase mRNA expression in the ventral mesencephalon but not in the hypothalamus. J Pineal Res 32:6-14. Summary: We have evaluated the effect of chronic administration of melatonin in terms of mRNA expression for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, and in the terms of dopamine (DA) transporter (DAT) by means of in situ hybridization. Experimental rats received daily late afternoon injections of 1.5 mg/kg melatonin for 30 days and analysis were performed in the ventral mesencephalon including the substantia nigra (SN) and ventral tegmental area (VTA), and hypothalamus. In the ventral mesencephalon, melatonin treatment significantly induced TH mRNA levels in individual dopaminergic neurons in SN and VTA. In contrast, DAT mRNA levels remained at control levels. Striatal synaptosomal DA uptake was not modified by melatonin treatment as compared with controls. Analysis of glutamic acid decarboxylase (GAD) mRNA in SN, the biosynthetic enzyme for GABAergic neurons, revealed no effect of melatonin treatment on mRNA levels for this marker. In the hypothalamus, we performed mRNA quantitation for TH in arcuate nucleus (Arc) and supraoptic nucleus (SO). Melatonin treatment failed to alter mRNA levels in either area. We detected weak but significant mRNA levels for DAT in Arc, SO, zona incerta (ZI) and periventricular hypothalamic nucleus (Pe). However, because of the low levels of mRNA in hypothalamic areas we were unable to perform a reliable measurement of DAT mRNA levels in response to melatonin treatment. We conclude that melatonin administration, that combines antioxidant capacity and a tissue-specific TH inducing effect, may be useful as a pharmacological agent to protect dopaminergic neurons from degeneration. Departamento de Bioquimica, Bromatologia, Toxicologia y Medicina Legal, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain.
• Baydas G, Nedzvetsky VS, Nerush PA, Kirichenko SV, Demchenko HM and Reiter RJ (2002). A novel role for melatonin: regulation of the expression of cell adhesion molecules in the rat hippocampus and cortex. Neurosci Lett 326:109-12. Summary: Neural cell adhesion molecules (NCAMs) are members of the immunoglobulin superfamily and are involved in synaptic rearrangements in the mature brain. There are three major NCAM forms: NCAM 180, NCAM 140 and NCAM 120. Several studies report that NCAMs play a central role in memory. In the present study we investigated the effects of melatonin on the expression of NCAMs in the hippocampus, cortex and cerebellum. The levels of NCAMs were determined by Western blotting. After administration of melatonin for 7 days, NCAM 180 expression increased both in the hippocampus and in the cortex as compared to controls. On the contrary, in rats exposed to the constant light for 7 days (which inhibits endogenous production of melatonin), NCAM 180 levels decreased in the hippocampus and became undetectable in cortex and cerebellum. NCAM 140 levels were also diminished in the hippocampus of constant light-exposed rats. There was no change in NCAM 120 expression in any brain regions. This is the first report indicating that melatonin has a modulatory effect on the expression of NCAM in brain areas concerned with cognitive function. Melatonin may be involved in structural remodeling of synaptic connections during memory and learning processes. Department of Physiology, College of Medicine, Firat University, Elazig 23119, Turkey. baydas@hotmail.com
• Pompeiano O, Manzoni D and Miele F (2002). Pineal gland hormone and idiopathic scoliosis: possible effect of melatonin on sleep-related postural mechanisms. Arch Ital Biol 140:129-58. Summary: Experimental and clinical evidences indicate that endocrine mechanisms, particularly involving the pineal gland, exert a role in the development of postural deficits leading to the occurrence of idiopatic scoliosis (IS). In particular, experiments performed in bipedal animals have shown that removal of the pineal gland, which secretes melatonin (M), induced a scoliosis, and that in such preparations, administration of this hormone prevented the development of this deformity (cf. 131). It appears also that adolescents with IS showed a reduced level of serum M with respect to age-related control subjects. The possible mechanisms involved in the M regulation of the tonic contraction of the axial musculature have been discussed. It is known that the pineal gland is implicated in the control of circadian rhythms, including the sleep-waking cycle, and that during this cycle there are prominent changes in postural activity, which affect not only the limbs, but also the axial musculature. These changes are characterized by a decrease followed by a suppression of postural activity, which occur particularly during transition from wakefulness to synchronized sleep and, more prominently, to rapid eye movement (REM) sleep. Episodes of postural atonia may also occur during the cataplectic episodes, which are typical of narcolepsy. Cholinergic and/or cholinoceptive neurons located in the dorsal pontine reticular formation (pRF) and the related medullary inhibitory reticulospinal (RS) system, intervene in the suppression of posture during REM sleep, as well as during the cataplectic episodes which occur in narcolepsy. These structures are under the modulatory (inhibitory) influence of the dorsomedial and the dorsolateral pontine tegmentum, where serotoninergic raphe nuclei (RN) neurons and noradrenergic locus coeruleus (LC) neurons are located. We postulated that M may act not only on the circadian pacemaker, but also directly on the pontine tegmental structures involved in the regulation of posture during the animal states indicated above. This hypothesis is supported by the facts that: 1) the dorsal pRF may contain specific binding sites for M; 2) this structure is particularly sensitive to M in adolescents, as well as in adult subjects affected by narcoleptic disturbances leading to cataplexy; 3) M increases the release of serotonin (5-HT), a neurotransmitter which enhances the postural tone by acting on the dorsal pRF: on the other hand, deficits in M levels may lower the activity of the serotoninergic raphe system, thus leading to a decrease or suppression of postural activity similar to that occurring either during REM sleep or during the cataplectic episodes typical of narcoleptic patients; 4) IS patients may show episodes of sleep apnea, a phenomenon which has been attibuted to a reduced tonic contraction of primary and accessory respiratory muscles during REM, resulting from a reduced release of 5-HT at dorsal pontine level. It has been postulated that, if the reduced M and 5-HT levels are subliminal to produce a complete suppression of posture under the conditions reported above, the reduced postural tone, which results from this condition may lead to the development of IS, due to hypotonia which affects the axial musculature. M secretion could be regulated not only by the activity of the serotoninergic raphe neurons projecting to the pineal gland, but probably also by the activity of noradrenergic LC neurons. It is likely that the development of IS, which results from a reduced level of M and 5-HT, may occur provided that the noradrenergic LC inhibition of the pontine structures is impaired. Such impairment could depend upon genetic factors, similar to those postulated to play a role in narcolepsy. In conclusion, the possibility exists that an impaired activity of brain monoaminergic systems may lead to disfunction in the production of M, which is apparently an important factor in the etiopathogenesis of IS. Dipartimento di Fisiologia e Biochimica, Universita di Pisa, Via S. Zeno 31, 1-56127 Pisa, Italy. pompeiano@dfb.unipi.it
• Venero JL, Absi el H, Cano J and Machado A (2002). Melatonin induces tyrosine hydroxylase mRNA expression in the ventral mesencephalon but not in the hypothalamus. J Pineal Res 32:6-14. Summary: We have evaluated the effect of chronic administration of melatonin in terms of mRNA expression for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, and in the terms of dopamine (DA) transporter (DAT) by means of in situ hybridization. Experimental rats received daily late afternoon injections of 1.5 mg/kg melatonin for 30 days and analysis were performed in the ventral mesencephalon including the substantia nigra (SN) and ventral tegmental area (VTA), and hypothalamus. In the ventral mesencephalon, melatonin treatment significantly induced TH mRNA levels in individual dopaminergic neurons in SN and VTA. In contrast, DAT mRNA levels remained at control levels. Striatal synaptosomal DA uptake was not modified by melatonin treatment as compared with controls. Analysis of glutamic acid decarboxylase (GAD) mRNA in SN, the biosynthetic enzyme for GABAergic neurons, revealed no effect of melatonin treatment on mRNA levels for this marker. In the hypothalamus, we performed mRNA quantitation for TH in arcuate nucleus (Arc) and supraoptic nucleus (SO). Melatonin treatment failed to alter mRNA levels in either area. We detected weak but significant mRNA levels for DAT in Arc, SO, zona incerta (ZI) and periventricular hypothalamic nucleus (Pe). However, because of the low levels of mRNA in hypothalamic areas we were unable to perform a reliable measurement of DAT mRNA levels in response to melatonin treatment. We conclude that melatonin administration, that combines antioxidant capacity and a tissue-specific TH inducing effect, may be useful as a pharmacological agent to protect dopaminergic neurons from degeneration. Departamento de Bioquimica, Bromatologia, Toxicologia y Medicina Legal, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain.
• Baydas G, Nedzvetsky VS, Nerush PA, Kirichenko SV, Demchenko HM and Reiter RJ (2002). A novel role for melatonin: regulation of the expression of cell adhesion molecules in the rat hippocampus and cortex. Neurosci Lett 326:109-12. Summary: Neural cell adhesion molecules (NCAMs) are members of the immunoglobulin superfamily and are involved in synaptic rearrangements in the mature brain. There are three major NCAM forms: NCAM 180, NCAM 140 and NCAM 120. Several studies report that NCAMs play a central role in memory. In the present study we investigated the effects of melatonin on the expression of NCAMs in the hippocampus, cortex and cerebellum. The levels of NCAMs were determined by Western blotting. After administration of melatonin for 7 days, NCAM 180 expression increased both in the hippocampus and in the cortex as compared to controls. On the contrary, in rats exposed to the constant light for 7 days (which inhibits endogenous production of melatonin), NCAM 180 levels decreased in the hippocampus and became undetectable in cortex and cerebellum. NCAM 140 levels were also diminished in the hippocampus of constant light-exposed rats. There was no change in NCAM 120 expression in any brain regions. This is the first report indicating that melatonin has a modulatory effect on the expression of NCAM in brain areas concerned with cognitive function. Melatonin may be involved in structural remodeling of synaptic connections during memory and learning processes. Department of Physiology, College of Medicine, Firat University, Elazig 23119, Turkey. baydas@hotmail.com