Decreased neurogenesis after cholinergic forebrain lesion in the adult rat.

• Adult neurogenesis has been shown to be regulated by a multitude of extracellular cues, including hormones, growth factors, and neurotransmitters. The cholinergic system of the basal forebrain is one of the key transmitter systems for learning and memory. Because adult neurogenesis has been implicated in cognitive performance, the present work aims at defining the role of cholinergic input for adult neurogenesis by using an immunotoxic lesion approach. The immunotoxin 192IgG-saporin was infused into the lateral ventricle of adult rats to selectively lesion cholinergic neurons of the cholinergic basal forebrain (CBF), which project to the two main regions of adult neurogenesis: the dentate gyrus and the olfactory bulb. Five weeks after lesioning, neurogenesis, defined by the number of cells colocalized for bromodeoxyuridine (BrdU) and the neuronal nuclei marker NeuN, declined significantly in the granule cell layers of the dentate gyrus and olfactory bulb. Furthermore, immunotoxic lesions to the CBF led to increased numbers of apoptotic cells specifically in the subgranular zone, the progenitor region of the dentate gyrus, and within the periglomerular layer of the olfactory bulb. We propose that the cholinergic system plays a survival-promoting role for neuronal progenitors and immature neurons within regions of adult neurogenesis, similar to effects observed previously during brain development. As a working hypothesis, neuronal loss within the CBF system leads not only to cognitive deficits but may also alter on a cellular level the functionality of the dentate gyrus, which in turn may aggravate cognitive deficits.

Nyckelord

Acetylcholine

metabolism

Animals

Antibodies

Monoclonal

Apoptosis

physiology

Basal Nucleus of Meynert

injuries

physiopathology

Brain Injuries

physiopathology

Cell Differentiation

physiology

Cell Division

physiology

Cholinergic Fibers

physiology

ultrastructure

Cognition Disorders

pathology

physiopathology

Dentate Gyrus

cytology

growth & development

Down-Regulation

physiology

Immunotoxins

Male

N-Glycosyl Hydrolases

Nerve Regeneration

physiology

Neural Pathways

injuries

physiopathology

Neuronal Plasticity

physiology

Olfactory Bulb

cytology

growth & development

Rats

Rats

Inbred F344

Ribosome Inactivating Proteins

Type 1

Stem Cells

cytology

physiology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)