Joseph Herbert
University of Cambridge, United Kingdom
Biography
Joseph Herbert is the Emeritus Professor of Neuroscience
in the University of Cambridge. He was the former director
of graduate training and previously, he was the coordinator
at Marie Curie Initial Training Network. His research areas
are: Neurochemical coding of behavioural and endocrine responses,
with reference to the action of neuropeptides and
steroids on adaptive responses. The cellular and molecular
action of neuropeptides. The neuro recording regulation of
hippocampal neurogenesis. The role of genes, stress, steroids,
amines and peptides in affective disorders. Neural and
genetic factors in the control of financial decision-making.
Abstract
Two of the most significant changes in hormones
with increasing age are those in cortisol and
dehydroepiandrosterone (DHEA). Cortisol levels tend
to increase and the daily cortisol rhythm is altered.
Both have potentially deleterious consequences for
the brain. Unlike its peripheral action, cortisol is proinflammatory
in the brain. Microglial activation, and the
consequent release of cytokines, alters the permeability
of the blood-brain barrier which removes some of
its regulatory and protective actions on the brain,
the constitution of the extracellular matrix, including
perineural networks, that play essential roles in synaptic
plasticity and memory, and in the formation of new cells
in the hippocampus, also a major component of the
mnemonic system. The actions of additional cortisol
are amplified by the coincident decrease in DHEA, a
prominent feature of ageing humans. DHEA moderates
the action of cortisol, including those on immune
function, inflammation and the rate of hippocampal
neurogenesis, but also has cellular actions of its own.
Astrocytes, because of their multiple influences on the
blood-brain barrier, extracellular matrix and synaptic
function, are major contributors to the process of
ageing in the brain. These steroids act both directly on
astrocytes, but also indirectly though their role on the
low-grade inflammation that characterises old age.
The combined change in these two hormones has
profound consequences for cognitive and emotional
function, including processing speed, executive
function, semantic, episodic and working memory (socalled
‘fluid’ domains), but also emotional recognition
and perception. Though age-related alterations in these
steroids are a general phenomenon, there are marked
individual differences in the rate at which they occur.
This may explain some of the corresponding individual
differences in brain function in older people.