Thyroid dysfunction is associated with cognitive impairment and dementia, including Alzheimer's disease (AD). It remains unclear whether thyroid dysfunction results from, or contributes to, Alzheimer pathology. We determined whether thyroid function is associated with dementia, specifically AD, and Alzheimer-type neuropathology in a prospective population-based cohort of Japanese-American men. Thyrotropin, total and free thyroxine were available in 665 men aged 71-93 years and dementia-free at baseline (1991), including 143 men who participated in an autopsy sub-study. During a mean follow-up of 4.7 (S.D.: 1.8) years, 106 men developed dementia of whom 74 had AD. Higher total and free thyroxine levels were associated with an increased risk of dementia and AD (age and sex adjusted hazard ratio (95% confidence interval) per S.D. increase in free thyroxine: 1.21 (1.04; 1.40) and 1.31 (1.14; 1.51), respectively). In the autopsied sub-sample, higher total thyroxine was associated with higher number of neocortical neuritic plaques and neurofibrillary tangles. No associations were found for thyrotropin. Our findings suggest that higher thyroxine levels are present with Alzheimer clinical disease and neuropathology.
The aim of the present study was to investigate the involvement of basal ganglia in altering respiration. The experiments were carried out on cats using the electrical stimulation techniques. The electrical stimulation of the basal ganglia caused locus-dependent changes both in the tidal volume and the rate of respiration. The most frequent effect of stimulation was hyperpnea and decrease in the tidal volume in awake, freely moving cats. An increase in the tidal volume appeared only as rebound-like aftereffect. The stimulation that caused hyperpnea in awake cats elicited smaller changes under chloralose or ketamine-induced anaesthesia, and, in certain cases, the stimulation produced apnea. After locally applied neurotoxic damage, the electrical stimulation failed to induce significant respiratory changes. It is suggested that the fast, small amplitude ventilation is, probably, produced by high excitation that shifts the respiratory rhythm generator towards the upper limits of its regulatory range. The slowing of ventilation might be produced by an inhibitory mechanism, which is able to cause even apnea under anaesthesia.
Neuronal modular (columnar) organisation of the cerebral cortex may represent an evolutionary acquisition that could optimize communication and information processing with the least volume compromise in terms of wiring. Yet, for such columns to be functionally operative adequate isolation from neighbouring units would be required, otherwise their spatial definition could be compromised. Evidence for "cable-like" processes stemming from astroglial cells has been recently presented although their existence has been forgotten for more than a century. These processes tend to form a sort of "palisade" or "brush" whose spatial distribution appears to correlate with the distribution of apical dendrites within the supragranular cortical layers. Patterned neuronal organization in the striate cortex is associated with a patterned distribution of GFAP-IR processes, both at the cellular and cell-aggregate levels. It can be tentatively proposed that evolutionary pressures resulted, in primates, in the progressive appearance of an increased length of astroglial processes in the supragranular region which may be associated with optimization of cerebral cortex modular (columnar) organization. It is interesting that this cortical region has undergone the larger growth among mammalian species during evolution, and would bear a crucial role in corticocortical interactions.
The purpose of the present study was to demonstrate the structural maturation of the horse brain in the critical period of development emergence of coordinated locomotion. Equine brains from 14 days before expected birth to adulthood were fixed in formaldehyde and embedded in paraffin. After taking the outer parameters of the brains, full series of large-area coronal sections were prepared on a special microtome and stained with Nissl's cresyl violet and Haidenhain's iron-haematoxylin. Microscopic images of sections were digitized and were subjected to computer-aided image analysis. The gross morphology of the brains and the image analysis of histological preparations suggest that in the perinatal period studied there is no substantial increase in brain size and mass, while the amount of Nissl substance and myelin grows rapidly till postnatal day 45. Then a relative decrease of both is observed till adulthood accompanied by a doubling of brain size and mass. It is concluded that during the maturation of the equine brain, decisive changes of the motor system such as up-regulation of protein sysnthesis and full myelination of motor tracts takes place during the critical period of onset of coordinated locomotion.
Potentiation of central cholinergic activity has been proposed as a therapeutic approach for improving the cognitive function in patients with Alzheimer's disease (AD). Increasing the acetylcholine concentration in the brain by modulating acetylcholine-sterase (AChE) activity is among the most promising therapeutic strategies. Efforts to treat the underlying pathology based on the modulation of amyloid precursor protein (APP) processing in order to decrease the accumulation of beta-amyloid are also very important. Alterations in APP metabolism have recently been proposed to play a key role in the long-lasting effects of AChE inhibitors. This review surveys recent data from in vivo and in vitro studies that have contributed to our understanding of the role of AChE inhibitors in APP processing. The regulatory mechanisms relating to the muscarinic agonist effect, protein kinase C activation and mitogen-activated protein kinase phosphorylation, involving the alpha-secretase or the 5 -UTR region of the APP gene, are also discussed. Further work is warranted to elucidate the exact roles in APP metabolism of the AChE inhibitors used in AD therapy at present.
Pineals from 6-day-old rats were transplanted into an incised bed of the parietal cortex of adult rats, of which 29 survived 4-5 weeks after transplantation. The pinealocytes and capillaries in the grafts were comparable in structure to those in the control. Grafts were demarcated from the host cortical tissue by a double, meninx plus gland-capsule sheath through which no nerve ingrowth was seen into the graft from the host brain. On the other hand, sympathetic nerves originating from the cervical ganglia reached the grafted pineal along the perivascular spaces of blood vessels, as is the case in situ. On this basis. the present meningeal graft is thought to be a model of the pineal gland surviving without its intracerebral neural control.
Lateral hypothalamus (LHA) plays a very important role in the modulation of nociceptive behaviour. The stimulation of LHA is known to produce analgesia of both tonic and phasic pain. The present study reports hyperalgesia induced by lateral hypothalamic lesions and the effect of fetal (gestation day 16) hypothalamic transplant on the nociceptive response to phasic thermal noxious stimulation [tail flick latency (TFL)] in LHA lesioned rats. The TFL decreased significantly (12.91 +/- 3.91 sec to 10.51+/- 1.23 sec) following LHA lesion. However, after transplantation, the TFL did not change. This is the first report of a hypothalamic transplant inducing recovery of a nociceptive response.
Background: In this report, we describe a new quantitative electron microscopic protocol based on the use of double colloidal-gold post-embedding immunostaining procedure as markers to analyze the subcellular distribution of enkephalin (ENK) and GABA neurotransmitters simultaneously in the same ultrathin tissue sections in the periaqueductal gray area (PAG) of the rat brain.Material and Methods: Double gold particle signals were significantly improved using a number of technical adjustments for the immunogold electron microscopic co-localization technique of ENK and GABA. The GABA-like neuronal elements were immuno-reacted with 20 nm gold particles and the enkephalin-like immunoreactive neurons were labeled with 10 nm gold particles. This double labeling was more apparent in tissue sections that were deactivated for the gold staining of the first antibody. Excellent double labeling was obtained when we blocked antigenicity of the first antiserum with hot (80 degrees C) paraformaldehyde fumes. To minimize the clumping of the second gold particles around the first gold particles used against the first antibody, we tried different staining order for the neurotransmitters tested in this study. It was necessary to use a detergent (Triton X-100) at very low concentration (0.1%) instead of etching to expose the antigenic determinants of the neurotransmitters and at the same time to reduce the deleterious effects on the morphology of the tissue sections. Furthermore, the high-glutaraldehyde fixation and the decrease in the interval between cutting and labeling of the ultrathin sections significantly improved the results obtained in this study.Results: Double labeling of sections with ENK and GABA produced co-localization in 23.1% and 1.2% of the immunoreactive axonal terminals and dendrites, respectively. Most of the double-labeled terminals contained more GABA-like than ENK-like immunolabeling. Half of the axon terminals [51%] and dendrites [56%] in the ventrolateral PAG were not labeled with either of GABA or ENK immunoreactivity.Conclusions: This procedure was found to be completely compatible with good double immunolabeling and ultrastructural preservation.
