title: The impact of mitochondrial aldehyde dehydrogenase (ALDH2) activation by Alda-1 on the behavioral and biochemical disturbances in animal model of depression.
abstract: The etiology of depression remains still unclear. Recently, it has been proposed, that mitochondrial dysfunction may be associated with development of mood disorders, such as depression, bipolar disorder and anxiety disorders. Mitochondrial aldehyde dehydrogenase (ALDH2), an enzyme responsible for the detoxification of reactive aldehydes, is considered to exert protective function in mitochondria. We investigated the influence of Alda-1, a small-molecule activator of ALDH2, on depressive- and anxiety-like behaviors in an animal model of depression - the prenatally stressed rats - using behavioral, molecular and proteomic methods. Prolonged Alda-1 administration significantly increased the climbing time, tended to reduce the immobility time and increased the swimming time of the prenatally stressed rats in the forced swim test. Moreover, treatment of prenatally stressed rats with Alda-1 significantly increased number of entries into the open arms of the maze and the time spent therein, as assessed by elevated plus-maze test. Such actions were associated with reduction of plasma 4-HNE-protein content, decrease of TNF-α mRNA and increase of PGC-1α (regulator of mitochondrial biogenesis) mRNA level in the frontal cortex and hippocampus of the prenatally stressed rats as well as with normalization of peripheral immune parameters and significant changes in expression of 6 and 4 proteins related to mitochondrial functions in the frontal cortex and hippocampus, respectively. Collectively, ALDH2 activation by Alda-1 led to a significant attenuation of depressive- and anxiety-like behaviors in the prenatally stressed rats. The pattern of changes suggested mitoprotective effect of Alda-1, however the exact functional consequences of the revealed alterations require further investigation.
authors.affiliation: Jagiellonian University Medical College, 31-531 Krakow, Poland.
authors.forename: Aneta
authors.initials: A
authors.lastname: Stachowicz
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Science, 31-343 Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Głombik
authors.affiliation: Jagiellonian University Medical College, 31-531 Krakow, Poland. Electronic address: mfolszan@cyf-kr.edu.pl.
authors.forename: Rafał
authors.initials: R
authors.lastname: Olszanecki
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Science, 31-343 Krakow, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Basta-Kaim
authors.affiliation: Jagiellonian University Medical College, 31-531 Krakow, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Suski
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Science, 31-343 Krakow, Poland.
authors.forename: Władysław
authors.initials: W
authors.lastname: Lasoń
authors.affiliation: Jagiellonian University Medical College, 31-531 Krakow, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Korbut
mesh_terms: D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000201:enzymology*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000008:administration & dosage; D052117:Benzodioxoles / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003866:Depressive Disorder / Q000201:enzymology*; D004195:Disease Models, Animal; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000201:enzymology* / Q000523:psychology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000201:enzymology* / Q000523:psychology*
chemical_list: D001549:Benzamides; D052117:Benzodioxoles; D016207:Cytokines; C531525:N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide; D012333:RNA, Messenger; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat
keywords: ALDH2; Alda-1; Behavior; Depression; Immunoreactivity; Mitochondria