Autism
ADHD
Bipolar Disorder
Brain
Parkinson/s
2008/2/11
Biochem Biophys Res Commun. 2007 Apr 27;356(1):200-6.
Epub 2007 Mar 5. Nishimura
K, Nakamura
K, Anitha A, Yamada
K, Tsujii M, Iwayama Y, Hattori
E, Toyota
T, Takei
N, Miyachi T, Iwata
Y, Suzuki
K, Matsuzaki H, Kawai
M, Sekine Y, Tsuchiya
K, Sugihara
G, Suda S, Ouchi Y, Sugiyama
T, Yoshikawa
T, Mori
N. Department
of Psychiatry and Neurology, Autism is a severe neurodevelopmental disorder defined by social and
communication deficits and ritualistic-repetitive behaviors that are detectable
in early childhood. Brain-derived neurotrophic
factor (BDNF) plays a critical role in the pathogenesis of autism. In this
study, we examined the SNP- and haplotypic-association
of BDNF with autism in a trios-based association study (the Autism Genetic
Resource Exchange). We also examined the expression of BDNF mRNA in the
peripheral blood lymphocytes of drug-naïve autism patients and control
subjects. In the TDT of autism trios, the SNP haplotype
combinations showed significant associations in the autism group. BDNF
expression in the drug-naïve autistic group was found to be significantly
higher than in the control group. We suggest that BDNF has a possible role
in the pathogenesis of autism through its neurotrophic
effects on the serotonergic system. PMID: 17349978 [PubMed
- indexed for MEDLINE] Behav Genet. 2007 May;37(3):487-97.
Epub 2007 Jan 10. Lasky-Su J, Faraone SV, Lange
C, Tsuang MT, Doyle
AE, Smoller JW, Laird
NM, Biederman J. Medical Genetics Research
Program, Department of Psychiatry and Behavioral Sciences, SUNY Upstate
Medical University, 750 East Adams Street, Syracuse, NY 13210, USA. Recent animal research suggests
that brain-derived neurotrophic factor (BDNF),
may mediate response to different environmental stimuli. In this paper, we
evaluated the possible role of BDNF as a moderator of attention deficit
hyperactivity disorder (ADHD) in the context of different socioeconomic
classes. We genotyped ten single nucleotide polymorphisms (SNPs) in and around BDNF in 229 families and evaluate
whether there are SNP-by-socioeconomic status (SES) interactions for
attention deficit hyperactivity. We developed three quantitative phenotypes
for ADHD from nine inattentive and nine hyperactive-impulsive symptoms that
were used in SNP-by-SES interaction analyses using a new methodology
implemented in the computer program PBAT. Findings were adjusted for
multiple comparisons using the false discovery rate. We found multiple
significant SNP-by-SES interactions using the inattentive symptom count.
This study suggests that different SES classes may modify the effect of the
functional variant(s) in and around BDNF to have an impact on the number of
ADHD symptom counts that are observed. The two exons
within BDNF represent potential functional variants that may be causing the
observed associations. PMID: 17216343 [PubMed
- indexed for MEDLINE] Neurosci Lett.
2007 Jun 8;420(1):45-48. Epub
2007 Apr 4. Gama CS, Andreazza AC, Kunz
M, Berk M, Belmonte-de-Abreu PS, Kapczinski F. Laboratório
de Psiquiatria Molecular, Centro de Pesquisas, Hospital de Clínicas
de Porto Alegre, Rua
Ramiro Barcelos, 2350, 90035 003, Porto Alegre, RS, Brazil; Programa
de Pós-Graduação em Medicina: Psiquiatria, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2400 – 2° andar,
90035 003, Porto Alegre, RS, Brazil;
Schizophrenia Program, Hospital de Clínicas de
Porto Alegre, Rua
Ramiro Barcelos, 2350, 90035 003, Porto Alegre, RS, Brazil. There is evidence that major
psychiatric discords such as schizophrenia (SZ) and bipolar disorder (BD)
are associated with dysregulation of synaptic
plasticity with downstream alterations of neurotrophins.
Brain-derived neurotrophic factor (BDNF) is the
most widely distributed neurotrophin in the
central nervous system (CNS), and performs many biological functions such
as promoting the survival, differentiation, and plasticity of neurons.
Variants in the BDNF gene increase the risk of SZ and bipolar disorder.
Chronic administration of drugs used to treat SZ and BD, such as lithium, valproate, quetiapine, clozapine, and olanzapine,
increases BDNF expression in rat brain. To examine serum BDNF, three groups
of chronically medicated DSM-IV SZ patients, on treatment with clozapine (n=27), typical (n=14), and other atypical antipsychotics (n=19), 30 euthymic
BD patients, and 26 healthy control had 5ml blood samples collected by venipuncture. Serum BDNF levels were significantly
higher in SZ patients (p<0.001) when compared to either controls or euthymic BD patients. Increased BDNF in SZ patients
might be related to the course of illness or to treatment variables.
Prospective studies are warranted. PMID: 17442489 [PubMed
- as supplied by publisher] J Neurosci. 2007
Oct 24;27(43):11533-42. Ahn M, Beacham D, Westenbroek RE, Scheuer T, Catterall WA. Department
of Pharmacology, Voltage-gated sodium channels are
responsible for action potential initiation and propagation in neurons, and
modulation of their function has an important impact on neuronal
excitability. Sodium channels are regulated by a Src-family
tyrosine kinase pathway, and this modulation can
be reversed by specifically bound receptor phosphoprotein
tyrosine phosphatase-beta. However, the specific
tyrosine kinase and signaling pathway are
unknown. We found that the sodium channels in rat brain interact with PMID: 17959796 [PubMed
- in process] J Mol Neurosci.
2007;33(3):239-51. Epub
2007 Apr 17. Forslin Aronsson
A, Spulber S, Oprica M, Winblad B, Post
C, Schultzberg M. Division of Neurodegeneration and Neuroinflammation,
Department of Neurobiology, Care Sciences and Society, Karolinska
Institutet, SE-141 86, Stockholm, Sweden, Stefan.Spulber@ki.se. This study investigates the
effects of alpha-melanocyte-stimulating hormone
(alpha-MSH), on neurodegeneration, gliosis and changes in the neurotrophic
protein brain-derived neurotrophic factor (BDNF)
and in pro-inflammatory cytokines, following kainic
acid (KA)-induced excitotoxic damage in the rat.
Male Sprague-Dawley rats were treated with
alpha-MSH (intraperitoneally, i.p.)
at 20 min, and 24 and 48 h following administration of 10 mg/kg KA (i.p.). The animals were sacrificed at 30 min, 4 h, 24 h
and 72 h after KA-administration and the levels of interleukin-1beta
(IL-1beta), interleukin-6 (IL-6) and tumour
necrosis factor-alpha (TNF-alpha) were analysed
in samples of hippocampus and hypothalamus. Levels of BDNF were analysed in the hippocampus. Stereological
quantification showed a markedly reduced number of viable neurons in the
CA1 pyramidal cell layer upon KA-administration as compared to animals
injected with vehicle (p < 0.05, 79,587 +/- 25,554 vs. 145,254 +/-
27,871). The number of viable neurons upon administration of alpha-MSH was
significantly higher than upon KA alone (p < 0.05, 119,776 +/- 33,158, KA+alpha-MSH vs. 79,587 +/- 27,554, KA + Saline). Astrocyte activation due to the KA-induced excitotoxicity was reduced, and the KA-induced increase
in IL-1beta levels was delayed by the treatment with alpha-MSH. In
conclusion, the degree of reduction in cell viability in the hippocampus
CA1 pyramidal cell layer upon KA-induced excitotoxicity
was similar to that seen previously upon global cerebral ischaemia. Furthermore, the administration of alpha-MSH
resulted in a similar increase in cell viability, supporting the hypothesis
that administration of alpha-MSH has rescuing effects on neurons subjected
to excitotoxic insults. PMID: 17952633 [PubMed
- in process] Brain Res.
2007 Sep 20; [Epub ahead of print] Chu NN, Zuo YF, Meng L, Lee
DY, Han
JS, Cui
CL. Neuroscience Research
Institute, The Ministry of Education and Ministry of Public Health, Peking
University, Beijing 100083, PR China; Department of Neurobiology, The
Ministry of Education and Ministry of Public Health, Peking University,
Beijing 100083, PR China; Key Laboratory of Neuroscience, The Ministry of
Education and Ministry of Public Health, Peking University, Beijing 100083,
PR China. Chronic morphine administration
induces functional and morphological alterations in the mesolimbic
dopamine system (MLDS), which is believed to be the neurobiological
substrate of opiate addiction. Our previous studies have demonstrated that
peripheral electrical stimulation (PES) can suppress morphine withdrawal
syndrome and morphine-induced conditioned place preference (CPP) in rats.
The present study was designed to investigate if PES could reverse the cell
size reduction induced by chronic morphine treatment in the ventral tegmental area (VTA), which is an important area of the
MLDS. Immunohistochemical observations showed
that the cell size of dopaminergic neurons in the
VTA reduced significantly in the chronic morphine-treated rats with a
concomitant decrease in the number of BDNF-positive cells compared to the
saline-treated rats. A much milder morphological change, accompanying with
an increased number of BDNF-positive cells, was observed in dopaminergic neurons in the rats that received repeated
100 Hz PES after morphine withdrawal. In another experiment, enzyme-linked immunosorbent assay (ELISA) reconfirmed a significant
up-regulation of BDNF protein level in the VTA in the rats received 100 Hz
PES after morphine abstinence. These results indicate that PES could
facilitate the morphological recovery of the VTA dopaminergic
cells damaged by chronic morphine treatment and up-regulate the BDNF protein
level in the VTA. Activation of endogenous BDNF by PES may play a role in
the recovery of the injured dopaminergic neurons
in the morphine addictive rats. PMID: 17945205 [PubMed
- as supplied by publisher] Wang
C, Bomberg E, Billington C, Levine
A, Kotz CM. Recent studies show that
brain-derived neurotrophic factor (BDNF)
decreases feeding and body weight after peripheral and ventricular
administration. BDNF mRNA and protein, and its receptor tyrosine kinase B (TrkB) are widely
distributed in the hypothalamus and other brain regions. However, there are
few reports on specific brain sites of actions for BDNF. We evaluated the
effect of BDNF in the hypothalamic paraventricular
nucleus (PVN) on feeding. BDNF injected unilaterally or bilaterally into
the PVN of food-deprived and nondeprived rats
significantly decreased feeding and body weight gain within the 0- to 24-h
and 24- to 48-h postinjection intervals.
Effective doses producing inhibition of feeding behavior did not establish
a conditioned taste aversion. PVN BDNF significantly decreased PVN neuropeptide Y (NPY)-induced feeding at 1, 2, and 4 h
following injection. BDNF administration in the PVN abolished food-restriction-induced
NPY gene expression in the hypothalamic arcuate
nucleus. In conclusion, BDNF in the PVN significantly decreases food intake
and body weight gain, suggesting that the PVN is an important site of
action for BDNF in its effects on energy metabolism. Furthermore, BDNF
appears to interact with NPY in its anorectic actions, although a direct
effect on NPY remains to be established. PMID: 17581841 [PubMed
- in process]] Mol Psychiatry. 2005 Oct;10(10):939-43. Association
of the paternally transmitted copy of common Valine
allele of the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene with susceptibility to
ADHD. Kent L, Green E, Hawi
Z, Kirley
A, Dudbridge
F, Lowe N, Raybould
R, Langley K,
Bray N, Fitzgerald M,
Owen MJ, O'Donovan MC,
Gill M, Thapar
A, Craddock N.
Developmental Psychiatry, Attention deficit hyperactivity disorder (ADHD) is a
common, highly heritable, neurodevelopmental
disorder with onset in early childhood. Genes involved in neuronal
development and growth are, thus, important etiological candidates and
brain-derived neurotrophic factor (BDNF), has
been hypothesized to play a role in the pathogenesis of ADHD. BDNF is a
member of the neurotrophin family and is involved
in the survival and differentiation of dopaminergic
neurons in the developing brain (of relevance because drugs that block the
dopamine transporter can be effective therapeutically). The common Val66Met
functional polymorphism in the human BDNF gene (rs
6265) was genotyped in a collaborative family-based sample of 341 white PMID: 15940292 [PubMed -
indexed for MEDLINE Dev Biol.
2003 Nov 15;263(2):216-30. Jourdi H, Iwakura Y, Narisawa-Saito M, Ibaraki
K, Xiong H, Watanabe
M, Hayashi
Y, Takei
N, Nawa H. Department
of Molecular Neurobiology, Brain Research Institute, Postsynaptic molecules with PDZ
domains (PDZ proteins) interact with various glutamate receptors and
regulate their subcellular trafficking and
stability. In rat neocortical development, the protein expression of
AMPA-type glutamate receptor GluR1 lagged behind its mRNA expression and
rather paralleled an increase in PDZ protein levels. One of the neurotrophins, brain-derived neurotrophic
factor (BDNF), appeared to contribute to this process, regulating the PDZ
protein expression. In neocortical cultures, BDNF
treatment upregulated SAP97, GRIP1, and Pick1 PDZ
proteins. Conversely, BDNF gene targeting downregulated these same PDZ molecules. The
BDNF-triggered increases in PDZ proteins resulted in the elevation of their
total association with the AMPA receptors GluR1 and GluR2/3, which led to
the increase in AMPA receptor proteins. When Sindbis
viruses carrying GluR1 or GluR2 C-terminal decoys disrupted their
interactions, GluR2 C-terminal decoys inhibited both BDNF-triggered GluR1
and GluR2/3 increases, whereas GluR1 C-terminal decoys blocked only the
BDNF-triggered GluR1 increase. In agreement, coexpression
of SAP97 and GluR1 in nonneuronal HEK293 cells
increased both proteins compared with their single transfection,
implying mutual stabilization. This work reveals a novel function of BDNF
in postsynaptic development by regulating the PDZ protein expression. PMID: 14597197 [PubMed
- indexed for MEDLINE] Kaufman
J, Yang
BZ, Douglas-Palumberi H, Grasso D, Lipschitz D, Houshyar S, Krystal JH, Gelernter
J. Child and Adolescent Research
and Education Program, Department of Psychiatry, Yale University School of
Medicine, New Haven, Connecticut 06511, USA. joan.kaufman@yale.edu BACKGROUND: Child abuse and genotype
interact to contribute to risk for depression in children. This study
examined gene-by-gene and gene-by-environment interactions. METHODS: The
study included 196 children: 109 maltreated and 87 nonmaltreated
comparison subjects. Measures of psychiatric symptomatology
and social supports were obtained using standard research instruments, and
serotonin transporter (5-HTTLPR) (locus SLC6A4) and brain-derived neurotrophic factor (BDNF) (variant val66met) genotypes
were obtained from saliva-derived DNA specimens. Population structure was
controlled by means of ancestral proportion scores computed based on
genotypes of ancestry informative markers in the entire sample. RESULTS:
There was a significant three-way interaction between BDNF genotype,
5-HTTLPR, and maltreatment history in predicting depression. Children with
the met allele of the BDNF gene and two short alleles of 5-HTTLPR had the
highest depression scores, but the vulnerability associated with these two
genotypes was only evident in the maltreated children. A significant
four-way interaction also emerged, with social supports found to further
moderate risk for depression. CONCLUSIONS: To the best of our knowledge,
this is the first investigation to demonstrate a gene-by-gene interaction
conveying vulnerability to depression. The current data also show a
protective effect of social supports in ameliorating genetic and
environmental risk for psychopathology. PMID: 16458264 [PubMed
- indexed for MEDLINE]
Genetic analyses of the brain-derived neurotrophic factor (BDNF) gene in autism.
A study of how socioeconomic status moderates
the relationship between SNPs encompassing BDNF
and ADHD symptom counts in ADHD families.
Serum levels of brain-derived neurotrophic factor in patients with schizophrenia and
bipolar disorder.
Regulation of Na(V)1.2
channels by brain-derived neurotrophic factor, TrkB, and associated
alpha-MSH Rescues
Neurons from Excitotoxic Cell Death.
Peripheral electrical stimulation reversed the
cell size reduction and increased BDNF level in the ventral tegmental area in chronic morphine-treated rats.
Brain-derived neurotrophic
factor in the hypothalamic paraventricular
nucleus reduces energy intake.
Brain-derived neurotrophic
factor signal enhances and maintains the expression of AMPA
receptor-associated PDZ proteins in developing cortical neurons.
Brain-derived neurotrophic factor-5-HTTLPR gene interactions and
environmental modifiers of depression in children.