Post by Max on Jun 30, 2005 6:16:16 GMT -5
Introduction
The (Ro)accutane induced degenerative process in the hippocampus are here suggested to be of two categories:
1) The suggested immediate continous degeneration during exposure, due to decreased cell survival and induced apoptosis or programmed cell death
2) The neuroendocrine condition after exposure, characterized by hormonal decline (including severe vitamin A deficiency), intracellular and extracellular changes, and the symptomatic implications post exposure (please see section 6 for suggested age related pathologies post (Ro)accutane exposure)
Suggested significant hippocampal cell loss during (Ro)accutane exposure in subjects
In a mouse model, endogenous RA generated by synthetic enzymes in the meninges acts on hippocampal granule neurons, and chronic (3-week) exposure to a clinical dose of 13-cis RA is suggested to result in hippocampal cell loss and supress hippocampal cell division and proliferation [3 and 4].
Vitamin A deficiency and effects on the hippocampus
Vitamin A deficiency may in itself, without a prior significant cell loss contribute to a worsened function of the hippocampus. Vitamin A deficiency was found to decrease hippocampal acethylcholine release. Following 12 weeks of vitamin A-free diet, rats were trained to acquire a radial-arm maze task. Results show that a vitamin A deficient diet induced a severe deficit in the spatial learning and memory task. A significant decrease in hippocampal acetylcholine release induced by scopolamine, assessed using microdialysis technique, and a reduction in the size of hippocampal nuclei of CA1 region in vitamin-deficient rats, compared to rats fed with a vitamin A-sufficient diet [7]. A decreased learning capacity was also found in the (Ro)accutane exposed rats [4]. In rats, dietary folic acid deficiency dramatically increased blood homocysteine levels and significantly reduced the number of proliferating cells in the dentate gyrus of the hippocampus in adult mice [8].
Effects of long-term thyroid deficiency on the hippocampus
In the hippocampus, neurotrophins are involved in the modulation of synaptic transmission, including the induction of long-term potentiation (LTP) through the receptor TrkB. The expression levels of two (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits, GluR2 and GluR3, but not GluR1 or GluR4, were found to be significantly altered in the hippocampus of p75NTR-deficient mice. These results implicate p75NTR in activity-dependent synaptic plasticity and extend the concept of functional antagonism of the neurotrophin signaling system. [1].
In postnatal rats, thyroxin is found to insert an important function in the regulation of Trk and p75NTR- signaling. After thyroxine application, the mRNA expression of neurotrophins of the nerve-growth-factor (NGF) family is significantly upregulated both in septum and hippocampus [2].
In a GH1 cell line, thyroid receptor expression is found to be suppressed by 50% in doses that could be expected in human subjects exposed to retinoic acid [5]. Inhibition of TR receptors, seems to be accompanied by inhibition of trkB receptors.
In an adult rat neuroblastoma cell line, induction of trkB mRNA is also caused by transient expression of either TR alpha 1 or beta 1 isoforms [6].
The function of the hippocampus
Neurogenesis in the adult hippocampus may play important roles in learning and memory, and in recovery from injury [9].
The (Ro)accutane induced degenerative process in the hippocampus are here suggested to be of two categories:
1) The suggested immediate continous degeneration during exposure, due to decreased cell survival and induced apoptosis or programmed cell death
2) The neuroendocrine condition after exposure, characterized by hormonal decline (including severe vitamin A deficiency), intracellular and extracellular changes, and the symptomatic implications post exposure (please see section 6 for suggested age related pathologies post (Ro)accutane exposure)
Suggested significant hippocampal cell loss during (Ro)accutane exposure in subjects
In a mouse model, endogenous RA generated by synthetic enzymes in the meninges acts on hippocampal granule neurons, and chronic (3-week) exposure to a clinical dose of 13-cis RA is suggested to result in hippocampal cell loss and supress hippocampal cell division and proliferation [3 and 4].
Vitamin A deficiency and effects on the hippocampus
Vitamin A deficiency may in itself, without a prior significant cell loss contribute to a worsened function of the hippocampus. Vitamin A deficiency was found to decrease hippocampal acethylcholine release. Following 12 weeks of vitamin A-free diet, rats were trained to acquire a radial-arm maze task. Results show that a vitamin A deficient diet induced a severe deficit in the spatial learning and memory task. A significant decrease in hippocampal acetylcholine release induced by scopolamine, assessed using microdialysis technique, and a reduction in the size of hippocampal nuclei of CA1 region in vitamin-deficient rats, compared to rats fed with a vitamin A-sufficient diet [7]. A decreased learning capacity was also found in the (Ro)accutane exposed rats [4]. In rats, dietary folic acid deficiency dramatically increased blood homocysteine levels and significantly reduced the number of proliferating cells in the dentate gyrus of the hippocampus in adult mice [8].
Effects of long-term thyroid deficiency on the hippocampus
In the hippocampus, neurotrophins are involved in the modulation of synaptic transmission, including the induction of long-term potentiation (LTP) through the receptor TrkB. The expression levels of two (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits, GluR2 and GluR3, but not GluR1 or GluR4, were found to be significantly altered in the hippocampus of p75NTR-deficient mice. These results implicate p75NTR in activity-dependent synaptic plasticity and extend the concept of functional antagonism of the neurotrophin signaling system. [1].
In postnatal rats, thyroxin is found to insert an important function in the regulation of Trk and p75NTR- signaling. After thyroxine application, the mRNA expression of neurotrophins of the nerve-growth-factor (NGF) family is significantly upregulated both in septum and hippocampus [2].
In a GH1 cell line, thyroid receptor expression is found to be suppressed by 50% in doses that could be expected in human subjects exposed to retinoic acid [5]. Inhibition of TR receptors, seems to be accompanied by inhibition of trkB receptors.
In an adult rat neuroblastoma cell line, induction of trkB mRNA is also caused by transient expression of either TR alpha 1 or beta 1 isoforms [6].
The function of the hippocampus
Neurogenesis in the adult hippocampus may play important roles in learning and memory, and in recovery from injury [9].