4_ Physiology(II) 動物福利生理學

Module 4
模組4
Physiological measures of
animal welfare (2):
動物福利之生理學測定法(二)
Neuroendocrine
神經內分泌系統
This module will enable you to
本模組的教學目標
• Understand the relationship between welfare
and physiology了解動物福利與生理學的關係
• Examine how the neuroendocrine system is
associated with welfare檢視神經內分泌系統與動
物福利之關係
• Understand how neuroendocrine responses
can be used to assess welfare了解如何利用神經
內分泌反應測量動物福利
• Identify some pros/cons of using
neuroendocrine measures to assess welfare
動物福利測量方法的正反理由
Review
複習模組3之內容
Change in welfare
動物福利改變
‫װ‬
Change in physical & psychological
states
生理及心理狀態改變
‫װ‬
Physiological responses
產生生理反應
Review
複習模組3之內容
Change in welfare
當動物福利改變時

Activation of CNS
中樞神經系統受刺激活化


Autonomic nervous
responses
Neuroendocrine
responses
自主神經系統反應
神經內分泌系統反應
Neuroendocrine system
關於神經內分泌系統
• A welfare change affects three subdivisions of the neuroendocrine system:
動物福利變化影響下列三個神經內分泌子系統:
– Hypothalamus 下視丘
– Pituitary gland 腦下垂體
– Adrenal gland 腎上腺
Hypothalamic-Pituitary-Adrenal
Axis (HPA)
下視丘-腦下垂體-腎上腺(HPA軸)
• Major mediator of endocrine responses內分泌反應
的主要媒介
• HPA increases mobilisation of energy stores for
physical response HPA加強動員儲存的能量,供生理
反應所需
• HPA mediates responses to: HPA調節的反應包括:
– Stress 壓力
─ Sexual activity 性行為
– Courtship 求偶 ─ Food arrival / foraging 尋覓食物
HPA cascade HPA軸作用流程
Hypothalamus 下視丘
腦下垂體前葉釋放激素
CRH
corticotrophin-releasing hormone
Anterior pituitary gland 腦下垂體前葉
促腎上腺皮質激素
ACTH adrenocorticotrophic hormone
Adrenal cortex 腎上腺皮質
糖皮質素
Glucocorticoids
Liver
Stimulus
刺激
肝臟
HAP vessels
下視丘前葉血管
Module 4
Circulation
血流
HPA characteristics
HPA軸之特性
• Response not as immediate as
sympathetic adreno-medullary system 反應
比交感腎上腺系統慢
• Measure of acute welfare changes 可測量
急性的動物福利變化
– For example, plasma glucocorticoids elevated
between 2-10 minutes after stimulation 動物在
受到刺激後2-10分鐘,糖皮質素的血中濃度提昇
– Can remain elevated for hours depending on
severity of stimulus 依照刺激的強弱,其濃度可以
在血中維持數小時
Glucocorticoid measurement
糖皮質素測量評估
Method
Invasive
Restrictive
Disturbing
方法
侵入性
限制性
干擾性
Plasma

 or 
 or 









血漿
Saliva
唾液
Urine
尿液
Faeces
糞便
Glucocorticoid measurement
糖皮質素測量評估
• Analytical methods 分析方法
– Enzyme-linked immunosorbent assay 酵素
連結免疫吸附分析
– High performance liquid chromatography
高壓液相層析分析
– Competitive protein binding assay 蛋白質結
合競爭分析
– Radioimmunoassay 同位素免疫分析
Glucocorticoids
糖皮質素
• Corticosterone: rodents, birds 囓齒、鳥類
• Cortisol: humans, pigs,
and monkeys 人類、豬、猴
• Useful direct measure
有用的直接測量準則
Glucocorticoid example 1
糖皮質素作用例1
• Cortisol  in lambs in response to:
– Tail-docking 小羊在實施斷尾
手術時糖皮質素會升高
– Castration小羊在實施閹割手
術時糖皮質素會升高
(Mellor & Murray, 1989)
Glucocorticoid example 2
糖皮質素作用—例二
• Urinary cortisol increases in
domestic dogs if they are put in
kennels 家犬隻若是被關入狗舍中,可
在尿液中檢測到cortisol濃度上升
(Hennessey et al 1997)
• If the dog has not been in
kennels before, the increase is
greater than if the dog has
experienced kennels before 而且
沒有被關入狗舍經驗的犬隻反應更激烈,
濃度上升越多 (Hiby 2005)
Chronic welfare assessment
慢性福利反應評估
• Indirect assessment of HPA 間接HPA評估法
• Glucocorticoid receptors in the brain 腦中糖皮
質素受體數目
– Number of receptors decreased in rats that were
exposed to prolonged handling and disturbance 大
鼠在經歷重複保定、驚擾的刺激後,發現腦中的受體
數量減少 (Wadham, 1997)
• ACTH challenge test 促腎上腺皮質素測試
– ACTH is administered, and resulting glucocorticoid
levels measured 注射ACTH後測血液中糖皮質素量
ACTH challenge test
促腎上腺皮質素測試
• Example: Dairy cows
以乳牛飼養為例
– Long periods of overcrowding => higher
cortisol response than
if less crowded 經長期
密飼後血中cortisol會升高
(Friend et al., 1977)
Limitations to HPA measures
HPA測量技術之限制
Individual differences: 個體差異
– Early experience 早年生活經驗
(Levine et al., 1967)
– Sex 性別
(Livezey et al., 1985)
– Metabolism 代謝狀態
Limitations to HPA measures
HPA測量技術之限制(續)
•
Species 物種
– New World Monkeys 新世界猴
(Klostermann et al., 1986)
•
Time when sampled 採樣時間
– Circadian rhythm 日夜規律
Limitations to HPA measures
HPA測量技術之限制(續)
•
Disturbance due to measurement 測量
之干擾
•
Human presence, handling, restraint
and sampling method 有人在動物旁邊、人
觸摸動物、保定,甚至是採樣方式不當
Other autonomic measures of
animal welfare
其他測量動物福利之項目
• Body temperature 體溫
• Opioid levels 類鴉片物質濃度
• Organ pathology 器官病理變化
Body temperature
體溫代表的意義
• Acute welfare measure 急性的福利測量
• Changes in other physiological systems (e.g.
adrenal activity) => changes in core body
temperature 其他生理系統產生變化(如腎上腺活性改變)
造成中心體溫出現改變
• Rat body temperature  by storms and unfamiliar
people 暴風與陌生人會使大鼠的體溫升高(Georgiev,
1978)
•  body temperature in defeated tree shrews 社會
地位挑釁落敗的樹鼩體溫反而下降(von Holst, 1986)
Temperature measurement
體溫測量
Method
Site
方法
採樣位置
Core
Temp
中心體溫
Direct, e.g.
thermometer
直接法--體溫計
Telemetry
嵌入遙測裝置
Thermoimaging
體表溫度照影
Invasi Restrictive Disturbing
ve
限制性
干擾性
侵入
性
Mouth,口
ear 耳 &
rectal 肛




Internal
體內


+/-
+/-
Skin
皮膚




Opioids
類鴉片類物質
• Three types 3種型式
– Endorphins 腦內啡
– Enkephalins 腦啡肽
– Dynorphins 強啡肽
• Functions: 功能
– Stress-induced analgesia 調適緊迫的止痛劑
– Control hormone release控制激素之分泌
Opioid measurement
類鴉片類之測量
Method
Invasive Restrictive
Disturbing
方法
侵入性
干擾性
Blood
血液
Brain receptors
腦內受體
限制性






Opioid examples
類鴉片類作用之實例
• Increase in plasma ß-endorphin in
lambs during castration, tail docking and
mulesing 綿羊在受閹割、斷尾、切臀皮時,血中ß腦內啡量會增加(Shutt et al.,1987)
• Tethered sows had higher opioid
receptor density than group-housed
sows 繫頸鏈的豬比群飼豬有較高之類鴉片類受體密
度(Zanella et al., 1996)
Organ Pathology
器官病變
• Chronic welfare changes => wide variety of
pathologies 慢性動物福利變化可造成多處器官病變
• Most are measured post-mortem e.g., 大部分
是藉由死後解剖來觀察,例如:
– Adrenal hypertrophy 腎上腺肥大
– Kidney lesions 腎臟病變
– Myocardial lesions 心肌病變
• In vivo 活體觀察
– Stomach ulcers 胃潰瘍
Pathology examples
器官病變之例
• Social instability in female groups of rats =
adrenal hypertrophy 置身於不安定社會之雌性大鼠
出現腎上腺肥大的病變(Haller et al., 1999)
• Subordinate mice show kidney lesions in the
presence of dominant animals 在強勢小鼠之存
在下,弱勢鼠產生腎臟的病變 (Henry & StephensLarson, 1985)
• Myocardial lesions associated with longer
periods of restraint in pigs 豬受到長期保定與心肌
病變有關 (Wutzen et al., 1987)
Conclusion
總結與討論
• Neuroendocrine system => acute and chronic
measures of welfare 神經內分泌系統可作為動物福
利之急性與慢性測量
• Direct and indirect ANS measures中樞神經系統
反應有直接與間接之測量
• Limitations of measures神經內分泌系統之測量有
其限制,故評估時要小心
• Other physiological responses can also be
used to assess welfare e.g. temperature,
organ pathology, and opioid levels 其他生理學
之反應亦可用來評估動物福利,包括體溫、器官之病理
變化、與血中類鴉片類濃度
Further reading
進階閱讀
• FRIEND, T.H., POLAN, C.E., GWAZDAUSKAS, F.C. & HEALD,
C.W., 1977: Adrenal glucocorticoid response to exogenous
adrenocorticotrophin mediated by density and social disruption in
dairy cows. J. Diary Sci. 60, 1958-1963
• GEORGIEV J. 1978 Influence of environmental conditions and
handling on temperature rhythm of the rat. Biotelemetry Patient
Monit. 5, 229-234
• HALLER J, FUCHS E, HALASZ J & MAKARA GB. 1999 Defeat is a
major stressor in males while social instability is stressful mainly in
females: Towards the development of a social stress model in
female rats. Brain Research Bulletin 50 (1): 33-39
• HENNESSEY MB, DAVIS HN, WILLIAMS MT, MELLOTT C &
DOUGLAS CW 1997 Plasma cortisol levels of dogs at a county
animal shelter. Physiol Behav 62: 485-490
Further reading
進階閱讀
• HENRYJP & STEPHENS-LARSON P. 1985 Specific aspects of
stress on disease processes. In: MOBERG, G. P. (Ed.) Animal Stress.
American Physiological Association, Maryland, USA
• HIBY EF 2005 The Welfare of Kennelled Domestic Dogs. PhD Thesis,
University of Bristol
• KALIN NH, CARNES M, BARKSDALE CM, SHELTON SE,
STEWART RD & RISCH SC. 1985 Effects of acute behavioural
stress on plasma and cerebrospinal fluid, ACTH and -endorphin in
rhesus monkeys. Neuroendocrinology 40, 97-101
• KLOSTERMANN LL, MURAI JT & SIITERI PK. 1986 Cortisol levels,
binding and properties of corticosteroid-binding globulin in the serum
of primates. Endocrinology 118, 424-434
• LANG RE, HEIL JWE, GANTEN D, HERMANN K & UNGER T. 1983
Oxytocin, unlike vasopressin, is a stress hormone in the rat.
Neuroendocrinology 37, 314-316
Further reading
進階閱讀
• LANE J 2006 Can non-invasive glucocorticoid measures be used as
reliable indicators of stress in animals? Animal Welfare 15: 331-342
• LEVINE S, HALTMEYER GC, KARAS GG & DENENBERG VH. 1969
Physiological and behavioural effects of infantile stimulation.
Physiology and Behavior 2, 55-59
• LIVEZEY GT, MILLER JM & VOGEL WH. 1985 Plasma
norepinephrine, epinephrine and corticosterone stress responses to
restraint in individual male and female rats and their correlations.
Neurosci. Lett. 62, 51-56
• MELLOR DJ & MURRAY L. 1989 Effects of tail docking and
castration on behaviour and plasma cortisol concentrations in young
lambs. Res. Vet. Sci. 46, 387-391
Further reading
進階閱讀
• SHUTT, D.A., FELL, L.R., CONNELL, R., BELL, A.K., WALLACE,
C.A. & SMITH, A.I., 1987: Stress-induced changes in plasma
concentrations of immunosuppressive ß-endorphin and cortisol in
response to routine surgical procedures in lambs. Aust. J. Biol. Sci.
40, 97-103.
• VON HOLST D. 1986 Vegetative and somatic components of tree
shrews’ behaviour. J. Auton. Nerv. Syst. Suppl., 657-670
• WADHAM JJB. 1997 Recognition and reduction of adverse effects
in research on rodents. PhD Thesis, Faculty of Medicine and
Dentistry, The University of Birmingham
• WUTZEN J, LEWICKI Z, ROZYCKA Z, CEREMUZYNSKI L &
BARCIKOWSKI R. 1987 Effects of immobilisation stress on
histological, histochemical and electron-microscopic changes in
porcine myocardium. Mat. Med. Pol. 19, 78-84.
• ZANELLA AJ, BROOM DM, HUNTER JC, MENDL MT. 1996 Brain
opioid receptors in relation to stereotypies, inactivity, and housing in
sows. Physiol Behav 59: 769-775