Neuropsychiatrische Störungen
Medizinische Studien zu Pregnenolon – Neuropsychiatrische Störungen
Pregnenolon übt nachweislich positive Effekte auf das Gehirn aus: Es verbessert beispielsweise das Gedächtnis und Lernen, hilft bei depressiven Störungen und unterstützt die Modulation kognitiver Funktionen.
Gedächtnisunterstützung in jedem Alter
Zahlreiche Forschungen der letzten 3 Jahrzehnte haben gezeigt, dass schon eine gering dosierte Pregnenolon-Zufuhr hilft, das Gedächtnis zu unterstützen, und dabei insbesondere das Langzeitgedächtnis. Zudem schützt Pregnenolon den Körper vor altersbedingten kognitiven Problemen und fördert gleichzeitig die Gesundheit des Nervensystems. Auch gesunde jüngere Menschen, die häufig Stresssituationen ausgesetzt sind, können übrigens von dieser Pregnenolon-Funktion profitieren, da diese Substanz eine optimale geistige Leistung unterstützt, indem sie neuronale Schäden vorbeugt.
Weitere Anwendungsgebiete
Geringere Pregnenolon-Werte als gesunde weisen auch Menschen auf, die an Depressionen, Angst- und Panikattacken, Schizophrenie oder Demenz, Psychosen und Dysfunktionen, die auf Cannabinoide zurückzuführen sind, leiden. Manche der positiven Wirkungen von Pregnenolon werden in Studien auf direkte Pregnenolon-Effekte zurückgeführt, andere wiederum entstehen durch die aus Pregnenolon metabolisierten Substanzen, wie DHEA, Progesteron und deren Derivate. Besonders interessant dabei ist die Tatsache, dass Pregnenolon die Neuroneogenese fördern kann, eine Eigenschaft, die insbesondere bei neurodegenerativen Erkrankungen genutzt werden kann.
Medizinische Studien zu Pregnenolon – Neuropsychiatrische Störungen
Molecular mechanisms of sex differences in epilepsy and seizure susceptibility in chemical, genetic and acquired epileptogenesis
2021-04 Reddy DS, Thompson W, Calderara G
This article provides a succinct overview of sex differences in epilepsy and putative molecular mechanisms underlying sex differences in seizure susceptibility in chemical, genetic, and acquired epileptogenesis.
TRPM3 in brain (patho)physiology
2021-02 Held K, Tóth BI
Already for centuries, humankind is driven to understand the physiological and pathological mechanisms that occur in our brains. Today, we know that ion channels play an essential role in the regulation of neural processes and control many functions of the central nervous system.
Allopregnanolone and pregnanolone are reduced in the hippocampus of epileptic rats, but only allopregnanolone correlates with seizure frequency
2021-01 Lucchi C, Costa AM, Rustichelli C, Biagini G
Neurosteroids modulate epileptic activity by interacting with the γ-aminobutyric acid type A receptor, but their brain levels are still undetermined.
Neurosteroids and focal epileptic disorders
2020-12 Lévesque M, Biagini G, Avoli M
Neurosteroids are a family of compounds that are synthesized in principal excitatory neurons and glial cells, and derive from the transformation of cholesterol into pregnenolone. The most studied neurosteroids-allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC)-are known to modulate GABAΑ receptor-mediated transmission, thus playing a role in controlling neuronal network excitability.
Longitudinal proneuroactive and neuroactive steroid profiles in medication-free women with, without and at-risk for perinatal depression: a liquid chromatography-tandem mass spectrometry analysis
2020-11 Deligiannidis KM, Kroll-Desrosiers AR, Tan Y, Dubuke ML, Shaffer SA
Neuroactive steroids (NAS) are derivatives of cholesterol or steroidal precursors made in the gonads, adrenal gland, placenta and brain. We characterized longitudinal plasma proneuroactive and NAS in healthy perinatal comparison women (HPCW), women at-risk for perinatal depression (AR-PND), and women with PND with/without comorbid anxiety. We hypothesized that AR-PND women who either did or did not go on to develop PND would have elevated NAS concentrations as compared to HPCW and that NAS would be correlated to depressive and anxiety symptoms.
Neurosteroids and seizure activity
2020-09 Miziak B, Chrościńska-Krawczyk M, Czuczwar SJ
Still circa 25% to 30% of patients with epilepsy cannot be efficiently controlled with available antiepileptic drugs so newer pharmacological treatment options have been continuously searched for. In this context, a group of endogenous or exogenous neurosteroids allosterically positively modulating GABA-A receptors may offer a promising approach.
Augmentation of endogenous neurosteroid synthesis alters experimental status epilepticus dynamics
2020-09 Lucchi C, Costa AM, Senn L, Messina S, Rustichelli C, Biagini G
Neurosteroids can modulate γ-aminobutyric acid type A receptor-mediated inhibitory currents. Recently, we discovered that the neurosteroids progesterone, 5α-dihydroprogesterone, allopregnanolone, and pregnanolone are reduced in the cerebrospinal fluid of patients with status epilepticus (SE). However, it is undetermined whether neurosteroids influence SE.
BV-2 microglial cells respond to rotenone toxic insult by modifying pregnenolone, 5α-dihydroprogesterone and pregnanolone levels
2020-09 Avallone R, Lucchi C, Puja G, Codeluppi A, Filaferro M, Vitale G, Rustichelli C, Biagini G
Neuroinflammation, whose distinctive sign is the activation of microglia, is supposed to play a key role in the development and progression of neurodegenerative diseases. The aim of this investigation was to determine levels of neurosteroids produced by resting and injured BV-2 microglial cells.
Steroids and Alzheimer’s disease: changes associated with pathology and therapeutic potential
2020-07 Akwa Y
Alzheimer’s disease (AD) is a multifactorial age-related neurodegenerative disease that today has no effective treatment to prevent or slow its progression. Neuroactive steroids, including neurosteroids and sex steroids, have attracted attention as potential suitable candidates to alleviate AD pathology.
Stress and drug abuse-related disorders: the promising therapeutic value of neurosteroids focus on pregnenolone-progesterone-allopregnanolone pathway
2019-10 Tomaselli G , Vallée M
The pregnenolone-progesterone-allopregnanolone pathway is receiving increasing attention in research on the role of neurosteroids in pathophysiology, particularly in stress-related and drug use disorders. These disorders involve an allostatic change that may result from deficiencies in allostasis or adaptive responses, and may be downregulated by adjustments in neurotransmission by neurosteroids.
TSPO ligands boost mitochondrial function and pregnenolone synthesis
2019-01 Lejri I, Grimm A, Hallé F, Abarghaz M, Klein C, Maitre M, Schmitt M, Bourguignon JJ, Mensah-Nyagan AG, Bihel F, Eckert A
Translocator protein 18 kDa (TSPO) is located in the mitochondrial outer membrane and plays an important role in steroidogenesis and cell survival. In the central nervous system (CNS), its expression is upregulated in neuropathologies such as Alzheimer’s disease (AD).
Neurosteroid levels in patients with bipolar disorder and a history of cannabis use disorders
2017-12 Van Enkevort E, Filbey F, Marx CE, Park J, Nakamura A, Sunderajan P, Brown ES
In animal models, levels of the neurosteroid pregnenolone increase after tetrahydrocannabinol (THC) administration and pregnenolone appears to attenuate the brain effects of THC. Given these interactions between pregnenolone and THC, we evaluated baseline neurosteroid levels in participants with a history of a cannabis use disorders (CUDs).
A role of endogenous progesterone in stroke cerebroprotection revealed by the neural-specific deletion of its intracellular receptors
2017-11 Zhu X, Fréchou M, Liere P, Zhang S, Pianos A, Fernandez N, Denier C, Mattern C, Schumacher M, Guennoun R
Treatment with progesterone protects the male and female brain against damage after middle cerebral artery occlusion (MCAO). However, in both sexes, the brain contains significant amounts of endogenous progesterone. It is not known whether endogenously produced progesterone enhances the resistance of the brain to ischemic insult.
Gender differences in susceptibility to schizophrenia: potential implication of neurosteroids
2017-10 Huang YC, Hung CF, Lin PY, Lee Y, Wu CC, Hsu ST, Chen CC, Chong MY, Lin CH, Wang LJ
Past research has indicated gender differences in the clinical characteristics and course of schizophrenia.
Uptake and metabolism of sulphated steroids by the blood-brain barrier in the adult male rat
2017-09 Qaiser MZ, Dolman DEM, Begley DJ, Abbott NJ, Cazacu-Davidescu M, Corol DI, Fry JP
Little is known about the origin of the neuroactive steroids dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulphate (PregS) in the brain or of their subsequent metabolism.
Pregnenolone does not interfere with the effects of cannabinoids on synaptic transmission in the cerebellum and the nucleus accumbens
2017-09 Krohmer A, Brehm M, Auwärter V, Szabo B
The steroid hormone pregnenolone attenuates several in vivo behavioural and somatic effects of the phytocannabinoid Δ9-tetrahydrocannabinol, and it was suggested that pregnenolone can protect the brain from cannabis intoxication.
Microtubule associated protein 2 in bipolar depression: impact of pregnenolone
2017-08 Daftary S, Yon JM, Choi EK, Kim YB, Bice C, Kulikova A, Park J, Sherwood Brown E
Pregnenolone, and related neurosteroids, may have antidepressant properties. Preclinical research proposes that microtubule associated protein 2 (MAP2) binding may be a mechanism for antidepressant properties of pregnenolone.
Adjunctive pregnenolone ameliorates the cognitive deficits in recent-onset schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial
2017-01 Kreinin A, Bawakny N, Ritsner MS
This study aimed to examine the effect of add-on treatment with the neurosteroid pregnenolone (PREG) on neurocognitive dysfunctions of patients with recent-onset schizophrenia (SZ) and schizoaffective disorder (SA).
Neurosteroids and potential therapeutics: focus on pregnenolone
2016-06 Vallée M
Considerable evidence from preclinical and clinical studies shows that steroids and in particular neurosteroids are important endogenous modulators of several brain-related functions.
Higher serum dehydroepiandrosterone sulfate protects against the onset of depression in the elderly: Findings from the English Longitudinal Study of Aging (ELSA)
2016-02 Souza-Teodoro LH, de Oliveira C, Walters K, Carvalho LA
Depression is one of the major causes of disability worldwide, but the complete etiology of depression is not fully understood. Dehydroepiandrosterone (DHEA) and its sulphated form DHEA(S) have been associated with mood and healthy aging.
The neurosteroids allopregnanolone and dehydroepiandrosterone modulate resting-state amygdala connectivity
2014-07 Sripada RK, Welsh RC, Marx CE, Liberzon I
The neurosteroids allopregnanolone and dehydroepiandrosterone (DHEA) are integral components of the stress response and exert positive modulatory effects on emotion in both human and animal studies.
Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: an 8-week, double-blind, randomized add-on two-center trial
2014-06 Ritsner MS, Bawakny H, Kreinin A
Management of recent-onset schizophrenia (SZ) and schizoaffective disorder (SA) is challenging owing to frequent insufficient response to antipsychotic agents. This study aimed to test the efficacy and safety of the neurosteroid pregnenolone in patients with recent-onset SZ/SA.
Pregnenolone can protect the brain from cannabis intoxication
2014-01 Vallée M, Vitiello S, Bellocchio L, Hébert-Chatelain E, Monlezun S, Martin-Garcia E, Kasanetz F, Baillie GL, Panin F, Cathala A, Roullot-Lacarrière V, Fabre S, Hurst DP, Lynch DL, Shore DM, Deroche-Gamonet V, Spampinato U, Revest JM, Maldonado R, Reggio PH, Ross RA, Marsicano G, Piazza PV
Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated.
Allopregnanolone elevations following pregnenolone administration are associated with enhanced activation of emotion regulation neurocircuits
2013-06 Sripada RK, Marx CE, King AP, Rampton JC, Ho S, Liberzon I
The neurosteroid allopregnanolone is a potent allosteric modulator of the gamma-aminobutyric acid type A receptor with anxiolytic properties. Exogenous administration of allopregnanolone reduces anxiety, and allopregnanolone blockade impairs social and affective functioning.
Pregnenolone for cognition and mood in dual diagnosis patients
2010-07 Osuji IJ, Vera-Bolaños E, Carmody TJ, Brown ES
Mood and substance-use disorders are both associated with cognitive deficits. Patients with mood and substance-use disorders have poorer cognition than patients with only a mood disorder. Pregnenolone may have beneficial effects on mood and cognition.
Neurosteroid regulation of central nervous system development
2007-10 Mellon SH
Neurosteroids are a relatively new class of neuroactive compounds brought to prominence in the past 2 decades.
Neuroactive steroids are altered in schizophrenia and bipolar disorder: relevance to pathophysiology and therapeutics
2006-06 Marx CE, Stevens RD, Shampine LJ, Uzunova V, Trost WT, Butterfield MI, Massing MW, Hamer RM, Morrow AL, Lieberman JA
Evidence suggests that neuroactive steroids may be candidate modulators of schizophrenia pathophysiology and therapeutics.
Microtubule-associated protein 2 (MAP2) is a neurosteroid receptor
2006-03 Fontaine-Lenoir V, Chambraud B, Fellous A, David S, Duchossoy Y, Baulieu EE, Robel P
The neurosteroid pregnenolone (PREG) and its chemically synthesized analog 3beta-methoxypregnenolone (MePREG) bind to microtubule-associated protein 2 (MAP2) and stimulate the polymerization of microtubules.