Histamine neurons in human hypothalamus: Anatomy in normal and alzheimer diseased brains

Ms, Airaksinen; Paetau, Anders; Paljärvi, Leo; Reinikainen, Kari; Riekkinen, Paavo; Suomalainen, R; Panula, Pertti

doi:10.1016/0306-4522(91)90070-5

Cited by 153 publications

(84 citation statements)

References 80 publications

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“…The basic structure and organization of the histaminergic system with all neurons in the posterior hypothalamic tuberomamillary nucleus in human brain are very similar to that of all other studied mammals (Airaksinen et al, 1991) (Fig. 3).…”

Section: Are the Models Relevant For Humansupporting

confidence: 59%

“…BF2.649, 1-{3-͓3-(4-chlorophenyl)propoxy͔propyl}piperidine hydrochloride; ABT-239, 4-(2-{2-͓(2R)-2-methylpyrrolidin-1-yl͔ethyl}-benzofuran-5-yl)benzonitrile; JNJ-10181457, 4-(3-(4-piperidin-1-ylbut-1-ynyl)benzyl)morpholine); VUF-5681, 4-͓3-(1H-imidazol-4-yl)propyl͔piperidine dihydrobromide. (Airaksinen et al, 1991). Each dot represents a cell in a 30-to 40-m-thick section stained with an antibody against histamine.…”

Section: Are the Models Relevant For Humanmentioning

confidence: 99%

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Histamine and H₃Receptor in Alcohol-Related Behaviors

Panula¹,

Nuutinen²

2010

J Pharmacol Exp Ther

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Data from rat models for alcohol preference and histidine decarboxylase knockout (HDC KO) mice suggest that brain histamine regulates alcohol-related behaviors. Histamine levels are higher in alcohol-preferring than in alcohol-nonpreferring rat brains, and expression of histamine H 3 receptor (H 3 R) is different in key areas for addictive behavior. H 3 R inverse agonists decrease alcohol responding in one alcohol-preferring rat line. Conditioned place preference induced by alcohol is stronger in HDC KO mice than in control mice. The HDC KO mice display a weaker stimulatory response to acute alcohol than the wildtype (WT) mice. In male inbred C57BL/6 mice the H 3 R antagonist ciproxifan inhibits ethanol-evoked stimulation of locomotor activity. Ciproxifan also potentiates the ethanol reward, but does not alone result in the development of place preference.At least in one rat model developed to study alcohol sensitivity high histamine levels are characteristic of the alcohol-insensitive rat line, and lowering brain histamine with a HDC inhibitor increases alcohol sensitivity in the tilting plane test. However, the motor skills of HDC KO mice do not seem to differ from those of the WT mice. Current evidence suggests that the histaminergic system is involved in the regulation of place preference behavior triggered by alcohol, possibly through an interaction with the mesolimbic dopamine system. Histamine may also interact with dopamine in the regulation of the corticostriato-pallido-thalamo-cortical motor pathway and cerebellar mechanisms, which may be important in different motor behaviors beyond alcohol-induced motor disturbances. H 3 R ligands may have significant effects on alcohol addiction. Rat Models of Alcohol-Related BehaviorsSeveral inbred and outbred rat lines with different alcohol preferences have been developed and reported (for a review, see Sinclair et al., 1989;Sommer et al., 2006). These include the high alcohol-preferring (HAP) and low alcohol-preferring (LAP) rats (Kitanaka et al., 2004), inbred alcohol-preferring and nonpreferring rats (McBride et al., 2010), and outbred alko alcohol (AA) and alko nonalcohol (ANA) rats (Sinclair et al., 1989;Sommer et al., 2006). A summary of rat and mouse models used in alcohol research is shown in Table 1.The AA and ANA rat lines were among the first lines produced using a bidirectional selection method (Eriksson, 1968) for alcohol preference, and these rats have now been maintained beyond the 100th generation (Sommer et al., 2006). The AA rats have higher levels of dopamine in several brain regions, including striatum and limbic forebrain, than the ANA rats (Ahtee and Eriksson, 1975), and tyrosine hydroxylase activity is also 42% higher in AA than ANA rats (Pispa et al., 1986). The levels of noradrenaline are also higher in AA rats than in ANA rats in the cortex and limbic areas (Ahtee and Eriksson, 1975). Noradrenaline turnover also appears higher in AA rats, because the levels of 3-methoxy-4-hydroxy-phenylglycol are higher in AA rats (Sommer et al.,...

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Section: Are the Models Relevant For Humansupporting

confidence: 59%

Section: Are the Models Relevant For Humanmentioning

confidence: 99%

Histamine and H₃Receptor in Alcohol-Related Behaviors

Panula¹,

Nuutinen²

2010

J Pharmacol Exp Ther

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“…Based on the effects of H 3 receptor blockade on scopolamine-induced amnesia and on retention of animals trained to avoid a footshock in repeated acquisition avoidance models of attention deficit hyperactivity disorder (ADHD) and other disorders in which vigilance and impulsivity are impaired (Fox et al, 2002), H 3 receptor antagonists were suggested as treatment for cognitive disorders, including Alzheimer's disease (AD) (Airaksinen et al, 1991;Nakamura et al, 1993). However, reduced brain histamine levels in AD (MazurkiewiczKwilecki and Nsonwah, 1989;Panula et al, 1998) have not been consistently demonstrated (Cacabelos et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Role of H3-Receptor-Mediated Signaling in Anxiety and Cognition in Wild-Type and Apoe–/– Mice

Bongers

Leurs

Robertson

et al. 2003

Neuropsychopharmacol

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Increasing evidence supports a role for histamine as a neurotransmitter and neuromodulator in emotion and cognition. The H 3 receptor was first characterized as an autoreceptor that modulates histamine release and synthesis via negative feedback. Mice deficient in apoE (Apoe -/-) have been used to define the role of apoE in brain function. In the present study, we investigated the possible role of histamine H 3 -receptor-mediated signaling in anxiety and cognition in mice Apoe -/-and wild-type mice. H 3 antagonists increased measures of anxiety in wild-type, but not Apoe -/-, mice. In contrast, H 3 antagonists similarly impaired object recognition in wild-type and Apoe -/-mice. In Apoe -/-mice, reduced negative feedback via H 3 receptors could contribute to increased signaling of H 1 receptors. Apoe -/-mice showed higher sensitivity to the anxiety-reducing effects of the H 1 receptor antagonist mepyramine than wild-type mice. These effects were dissociated from effects of mepyramine on the HPA axis. Compared to saline controls, mepyramine reduced plasma ACTH and corticosterone levels in wild-type, but not Apoe -/-, mice. These data support a role for apoE in H 3 receptor signaling. H 3 antagonists were proposed as a treatment for cognitive disorders such as Alzheimer's disease, which is associated with increased anxiety and cognitive impairments. As H 3 antagonists increase measures of anxiety and impair object recognition in wild-type mice, the use of H 3 antagonists in cognitive disorders may be counterproductive and should be carefully evaluated.

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“…Schneider et al (1997) reported that the level of histidine decarboxylase, the enzyme responsible for converting histidine to histamine, was decreased approximately 50% in the frontal cortex of patients with AD. Airaksinen et al (1991) reported that, in patients with AD, large numbers of large globular neurofibrillary tangles were found in the tuberomammillary neurons of the hypothalamus. Histaminergic neurons arise from the tuberomammillary nucleus within the hypothalamus and project throughout the brain, where they modulate the release of various neurotransmitters, including ACh.…”

Section: Introductionmentioning

confidence: 99%

The 5-Hydroxytryptamine₄ Receptor Agonists Prucalopride and PRX-03140 Increase Acetylcholine and Histamine Levels in the Rat Prefrontal Cortex and the Power of Stimulated Hippocampal θ Oscillations

Johnson

Drummond²,

Grimwood³

et al. 2012

J Pharmacol Exp Ther

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5-Hydroxytryptamine (5-HT) 4 receptor agonists reportedly stimulate brain acetylcholine (ACh) release, a property that might provide a new pharmacological approach for treating cognitive deficits associated with Alzheimer's disease. The purpose of this study was to compare the binding affinities, functional activities, and effects on neuropharmacological responses associated with cognition of two highly selective 5-HT 4 receptor agonists, prucalopride and 6,7-dihydro-4-hydroxy-7-isopropyl-6-oxo-N-[3-(piperidin-1-yl)propyl]thieno[2,3-b]pyridine-5-carboxamide (PRX-03140). In vitro, prucalopride and PRX-03140 bound to native rat brain 5-HT 4 receptors with K i values of 30 nM and 110 nM, respectively, and increased cAMP production in human embryonic kidney-293 cells expressing recombinant rat 5-HT 4 receptors. In vivo receptor occupancy studies established that prucalopride and PRX-03140 were able to penetrate the brain and bound to 5-HT 4 receptors in rat brain, achieving 50% receptor occupancy at free brain exposures of 330 nM and 130 nM, respectively. Rat microdialysis studies revealed that prucalopride maximally increased ACh and histamine levels in the prefrontal cortex at 5 and 10 mg/kg, whereas PRX-03140 significantly increased cortical histamine levels at 50 mg/kg, failing to affect ACh release at doses lower than 150 mg/kg. In combination studies, donepezil-induced increases in cortical ACh levels were potentiated by prucalopride and PRX-03140. Electrophysiological studies in rats demonstrated that both compounds increased the power of brainstem-stimulated hippocampal oscillations at 5.6 mg/kg. These findings show for the first time that the 5-HT 4 receptor agonists prucalopride and PRX-03140 can increase cortical ACh and histamine levels, augment donepezil-induced ACh increases, and increase stimulated-hippocampal power, all neuropharmacological parameters consistent with potential positive effects on cognitive processes.

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Histamine neurons in human hypothalamus: Anatomy in normal and alzheimer diseased brains

Cited by 153 publications

References 80 publications

Histamine and H₃Receptor in Alcohol-Related Behaviors

Histamine and H₃Receptor in Alcohol-Related Behaviors

Role of H3-Receptor-Mediated Signaling in Anxiety and Cognition in Wild-Type and Apoe–/– Mice

The 5-Hydroxytryptamine₄ Receptor Agonists Prucalopride and PRX-03140 Increase Acetylcholine and Histamine Levels in the Rat Prefrontal Cortex and the Power of Stimulated Hippocampal θ Oscillations

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Histamine neurons in human hypothalamus: Anatomy in normal and alzheimer diseased brains

Cited by 153 publications

References 80 publications

Histamine and H3Receptor in Alcohol-Related Behaviors

Histamine and H3Receptor in Alcohol-Related Behaviors

Role of H3-Receptor-Mediated Signaling in Anxiety and Cognition in Wild-Type and Apoe–/– Mice

The 5-Hydroxytryptamine4 Receptor Agonists Prucalopride and PRX-03140 Increase Acetylcholine and Histamine Levels in the Rat Prefrontal Cortex and the Power of Stimulated Hippocampal θ Oscillations

Contact Info

Product

Resources

About

Histamine and H₃Receptor in Alcohol-Related Behaviors

Histamine and H₃Receptor in Alcohol-Related Behaviors

The 5-Hydroxytryptamine₄ Receptor Agonists Prucalopride and PRX-03140 Increase Acetylcholine and Histamine Levels in the Rat Prefrontal Cortex and the Power of Stimulated Hippocampal θ Oscillations