Benzodiazepine Receptors in the Periphery

2020 ◽  
pp. 81-96
Author(s):  
Robert B. Raffa
Keyword(s):  
Immune Function ◽  
Cholesterol Metabolism ◽  
Benzodiazepine Receptors ◽  
Benzodiazepine Receptor ◽  
Peripheral Benzodiazepine Receptor ◽  
Pharmacologic Effect ◽  
Ion Influx ◽  
Transmembrane Potential Difference ◽  
The Brain

The benzodiazepines are almost universally thought to produce one and only one pharmacologic effect: positive allosteric modulation of GABAA receptors located in the brain. This results in an increased Cl−ion influx, greater negative transmembrane potential difference, and neurons that are less likely to fire in response to anxiety-producing stimulation. Unfortunately, the simplicity and success of this mono-target belief has distracted researchers and clinicians from studying and appreciating their other pharmacology. A glaring example is the general lack of awareness of the peripheral benzodiazepine receptor. The peripheral benzodiazepine receptor alters mitochondrial function (energy supply), cholesterol transport, and immune function. A patient who is on long-term benzodiazepine therapy (or withdrawing from them) will have these sites affected, just as are the sites located in the brain. One can easily imagine that the adverse effects associated with the peripheral sites would be fundamental, varied, and potentially profound—involving lack of energy, altered cholesterol metabolism, and aberrant immune function.

Different effects of long-term haloperidol administration on GABAA and benzodiazepine receptors in various parts of the brain

1986 ◽  
Vol 101 (4) ◽  
pp. 460-463 ◽  
Author(s):  
�. �. Vasar ◽  
A. M. Nurk ◽  
M. O. Maimets ◽  
A. H. Soosaar ◽  
L. H. Allikmets
Keyword(s):  
Benzodiazepine Receptors ◽  
The Brain

scholarly journals Serum 24S-hydroxycholesterol predicts long-term brain structural and functional outcomes after hypoxia-ischemia in neonatal mice

2020 ◽  
pp. 0271678X2091191 ◽  
Author(s):  
Fuxin Lu ◽  
Shujuan Fan ◽  
Andrea R Romo ◽  
Duan Xu ◽  
Donna M Ferriero ◽  
...  
Keyword(s):  
Brain Damage ◽  
Functional Outcomes ◽  
Cholesterol Metabolism ◽  
Blue Staining ◽  
Functional Impairments ◽  
Major Pathway ◽  
Hypoxia Ischemia ◽  
Severe Motor ◽  
The Brain

The major pathway of brain cholesterol turnover relies on its hydroxylation into 24S-hydroxycholesterol (24S-HC) using brain-specific cytochrome P450 46A1 (CYP46A1). 24S-HC produced exclusively in the brain normally traverses the blood-brain barrier to enter the circulation to the liver for excretion; therefore, the serum 24S-HC level is an indication of cholesterol metabolism in the brain. We recently reported an upregulation of CYP46A1 following hypoxia-ischemia (HI) in the neonatal mouse brain and a correlation between serum 24S-HC levels and acute brain damage. Here, we performed a longitudinal study to investigate whether the serum 24S-HC concentrations predict long-term brain structural and functional outcomes. In postnatal day 9 mice subjected to HI, the serum 24S-HC levels increased at 6 h and 24 h after HI and correlated with the infarct volumes measured histologically or by T2-weighted MRI. The 24 h levels were associated with white matter volume loss quantified by MBP immunostaining and luxol fast blue staining. The animals with higher serum 24S-HC at 6 h and 24 h corresponded to those with more severe motor and cognitive deficits at 35-40 days after HI. These data suggest that 24S-HC could be a novel and early blood biomarker for severity of neonatal HI brain damage and associated functional impairments.

The Benzodiazepine Receptor in Normal and Pathological Human Brain

1978 ◽  
Vol 133 (3) ◽  
pp. 261-268 ◽  
Author(s):  
H. Möhler ◽  
T. Okada
Keyword(s):  
Central Nervous System ◽  
Membrane Fraction ◽  
Benzodiazepine Receptors ◽  
Benzodiazepine Receptor ◽  
Synaptic Membrane ◽  
Huntington's Chorea ◽  
High Affinity ◽  
Cortical Areas ◽  
The Central Nervous System ◽  
The Brain

SummaryBenzodiazepines bind with high affinity to a specific benzodiazepine receptor, which occurs exclusively in the central nervous system. The affinity of various benzodiazepines to the receptor closely parallels their pharmacological and therapeutic potency. Binding to the receptor is stereospecific. The receptor is mainly localized in the synaptic membrane fraction and has its highest density in cortical areas of the brain. In Huntington's chorea a decrease in benzodiazepine receptor binding is found in caudate nucleus and putamen, which, at least in putamen, is due to a loss of benzodiazepine receptors apparently located on GABA neurones, which degenerate in Huntington's chorea. The loss of benzodiazepine receptors might explain why the ameliorative effects of benzodiazepines in the early stages of the disease are not sustained in the later stages.

Stress-induced norepinephrine release in the rat prefrontal cortex measured by microdialysis

1994 ◽  
Vol 267 (6) ◽  
pp. R1559-R1566 ◽  
Author(s):  
H. Nakane ◽  
N. Shimizu ◽  
T. Hori
Keyword(s):  
Prefrontal Cortex ◽  
Benzodiazepine Receptors ◽  
Benzodiazepine Receptor ◽  
Intracerebral Microdialysis ◽  
Fg 7142 ◽  
Basal Release ◽  
Benzodiazepine Receptor Agonist ◽  
Series Of Experiments ◽  
Medial Pfc ◽  
The Brain

Norepinephrine (NE) release in the medial prefrontal cortex (PFC) of rats was studied during immobilization using an intracerebral microdialysis technique. A series of experiments using pharmacological and physiological manipulations indicated that the NE recovered in the medial PFC dialysate was mainly derived from nerve terminals and that the dorsal noradrenergic bundle was a major source of NE in the medial PFC. Immobilization stress immediately elevated NE levels to 176.0 +/- 9.0% of basal release, and this increase continued for the entire period of stress and 20 min after termination of the stress. Preinjection of a benzodiazepine receptor agonist, diazepam (5 mg/kg ip), significantly attenuated immobilization-induced NE release, while injection of an anxiogenic compound, FG-7142 (20 mg/kg ip), facilitated NE release in an obviously nonstressed condition. These results therefore suggest that stressful stimuli activate the NE system in the medial PFC, which may be modulated by an activation of benzodiazepine receptors in the brain.

Novel peripheral benzodiazepine receptor ligand [11C]DAA1106 for PET: An imaging tool for glial cells in the brain

Synapse ◽  
2004 ◽  
Vol 52 (4) ◽  
pp. 283-291 ◽  
Author(s):  
Jun Maeda ◽  
Tetsuya Suhara ◽  
Ming-Rong Zhang ◽  
Takashi Okauchi ◽  
Fumihiko Yasuno ◽  
...  
Keyword(s):  
Glial Cells ◽  
Benzodiazepine Receptor ◽  
Peripheral Benzodiazepine Receptor ◽  
Receptor Ligand ◽  
Imaging Tool ◽  
The Brain

The Acute Effect of Alcohol on Various Memory Processes

2010 ◽  
Vol 24 (4) ◽  
pp. 249-252 ◽  
Author(s):  
Márk Molnár ◽  
Roland Boha ◽  
Balázs Czigler ◽  
Zsófia Anna Gaál
Keyword(s):  
Low Dose ◽  
Short Term Memory ◽  
Acute Effect ◽  
Long Term Memory ◽  
Term Memory ◽  
Memory Processes ◽  
Different Types ◽  
The Brain ◽  
Legal Consequences

This review surveys relevant and recent data of the pertinent literature regarding the acute effect of alcohol on various kinds of memory processes with special emphasis on working memory. The characteristics of different types of long-term memory (LTM) and short-term memory (STM) processes are summarized with an attempt to relate these to various structures in the brain. LTM is typically impaired by chronic alcohol intake but according to some data a single dose of ethanol may have long lasting effects if administered at a critically important age. The most commonly seen deleterious acute effect of alcohol to STM appears following large doses of ethanol in conditions of “binge drinking” causing the “blackout” phenomenon. However, with the application of various techniques and well-structured behavioral paradigms it is possible to detect, albeit occasionally, subtle changes of cognitive processes even as a result of a low dose of alcohol. These data may be important for the consideration of legal consequences of low-dose ethanol intake in conditions such as driving, etc.

Moving past the vaccine/autism controversy - to examine potential vaccine neurological harms

2020 ◽  
pp. 1-15
Author(s):  
Peter R. Breggin
Keyword(s):  
Neurological Disorders ◽  
Developmental Disorder ◽  
Physical Symptoms ◽  
Psychosocial Disorders ◽  
The Us ◽  
Potential Vaccine ◽  
Research And Education ◽  
The Brain ◽  
New Vaccines

BACKGROUND: The vaccine/autism controversy has caused vast scientific and public confusion, and it has set back research and education into genuine vaccine-induced neurological disorders. The great strawman of autism has been so emphasized by the vaccine industry that it, and it alone, often appears in authoritative discussions of adverse effects of the MMR and other vaccines. By dismissing the chimerical vaccine/autism controversy, vaccine defenders often dismiss all genuinely neurological aftereffects of the MMR (measles, mumps, and rubella) and other vaccines, including well-documented events, such as relatively rare cases of encephalopathy and encephalitis. OBJECTIVE: This report explains that autism is not a physical or neurological disorder. It is not caused by injury or disease of the brain. It is a developmental disorder that has no physical origins and no physical symptoms. It is extremely unlikely that vaccines are causing autism; but it is extremely likely that they are causing more neurological damage than currently appreciated, some of it resulting in psychosocial disabilities that can be confused with autism and other psychosocial disorders. This confusion between a developmental, psychosocial disorder and a physical neurological disease has played into the hands of interest groups who want to deny that vaccines have any neurological and associated neuropsychiatric effects. METHODS: A review of the scientific literature, textbooks, and related media commentary is integrated with basic clinical knowledge. RESULTS: This report shows how scientific sources have used the vaccine/autism controversy to avoid dealing with genuine neurological risks associated with vaccines and summarizes evidence that vaccines, including the MMR, can cause serious neurological disorders. Manufacturers have been allowed by the US Food and Drug Administration (FDA) to gain vaccine approval without placebo-controlled clinical trials. CONCLUSIONS: The misleading vaccine autism controversy must be set aside in favor of examining actual neurological harms associated with vaccines, including building on existing research that has been ignored. Manufacturers of vaccines must be required to conduct placebo-controlled clinical studies for existing vaccines and for government approval of new vaccines. Many probable or confirmed neurological adverse events occur within a few days or weeks after immunization and could be detected if the trials were sufficiently large. Contrary to current opinion, large, long-term placebo-controlled trials of existing and new vaccines would be relatively easy and safe to conduct.

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